IBS-KAI-KSV Conference on
Infection and Immunity
July 17 – 19, 2024
2F, Grand Ballroom, Daejeon Convention Center 1 (DCC 1), Daejeon, South Korea
Welcome to the IBS-KAI-KSV Conference on Infection and Immunity
“IBS-KAI-KSV Conference on Infection and Immunity” aims to bring together professionals and experts from various fields to exchange ideas, insights, and experiences on Infection and Immunity area. With a diverse range of speakers, interactive sessions, and networking opportunities, the conference promises to be both informative and engaging.
Date & Venue
July 17th – 19th, 2024
2F, Grand Ballroom ,Daejeon Convention Center 1 (DCC 1), Daejeon, South Korea
Program
| 12:30-13:00 | Opening Remarks
|
| Session 1: Advanced in Viral Pathogenesis / Chair: Kyun-Hwan Kim, Sanghyun Lee |
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| 13:00-13:50 | Yoshihiro Kawaoka (National Center for Global Health and Medicine, Japan / University of Tokyo, Japan / University of Wisconsin-Madison, USA) Addressing the threat of emerging viral infections |
| 13:50-14:20 | Kyun-Hwan Kim (Sungkyunkwan University, Korea) Viral escape mechanisms against IFN-induced host defense |
| 14:20-14:50 | Sanghyun Lee (Brown University, USA) Intestinal immune modulation by norovirus |
| 14:50-15:20 | SangJoon Lee (Ulsan National Institute of Science and Technology, Korea) Discovery of inflammasome sensors in viral infections |
| 15:20-15:50 | Break |
| Session 2: Novel Strategies for Controls of Viral Diseases / Chair: Jinjong Myoung, Hye-Ra Lee |
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| 15:50-16:30 | YI Guan (The University of Hong Kong, Hong Kong) Origin and Emerging of COVID-19 |
| 16:30-17:00 | Jinjong Myoung (Jeonbuk National University, Korea) Reverse genetics-based vaccines against SARS-CoV-2 |
| 17:00-17:30 | Yong Taik Lim (Sungkyunkwan University, Korea) Engineered nano-vaccines for prolonged and broad protection against heterologous variants of SARS-CoV-2 and influenza virus |
| 17:30-18:00 | Hye-Ra Lee (Korea University, Korea) EndMT by intracellular Acetyl-CoA flux occurs the disseminated visceral Kaposi’s sarcoma |
| Session 3: Novel Tick-Borne viral Diseases / Chair: Young Ki Choi, Meehyein Kim |
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| 09:30-10:10 | Jae Ung Jung (Cleveland Clinic, USA) Intervention Approach of Emerging Viruses |
| 10:10-10:40 | Young Ki Choi (Korea Virus Research Institute, Korea) Age-dependent different pathogenesis of viral diseases |
| 10:40-11:10 | Aihua Zheng (Chinese Academy of Sciences, China) Natural circulation and spread of Severe fever with thrombocytopenia syndrome virus |
| 11:10-11:40 | Nam-Hyuk Cho (Seoul National University, Korea) Hematopoietic dysregulation in Severe Fever with Thrombocytopenia Syndrome |
| 11:40-12:10 | Meehyein Kim (KRICT, Korea) Discovery of novel antiviral compounds targeting 3CL protease of SARS-CoV-2 |
| 12:10-13:25 | Lunch |
| 13:25-13:30 | Congratulatory Remarks
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| Session 4: Immunology 1 / Chair: Eui-Cheol Shin, Martin Prlic | |
| 13:30-14:10 | Kanta Subbarao (Laval University, Canada) Zoonotic, Pandemic and Endemic Coronaviruses |
| 14:10-14:40 | Je-Min Choi (Hanyang University, Korea) The heterogeneity of steady-state CD4 T cells and their impact on cytokine-dependent bystander response in autoimmune disease and cancer |
| 14:40-15:10 | Ross M. Kedl (University of Colorado Anschutz Medical Campus, USA) Mechanisms of Adjuvant-Elicited Cellular Immunity not revealed by infectious biology |
| 15:10-15:40 | Break |
| Session 5: Immunology 2 / Chair: Je-Min Choi, Ross M. Kedl |
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| 15:40-16:10 | Hye-Jung Kim (Genentech, USA) CD8 Treg mediated immune regulation in inflammation |
| 16:10-16:40 | Martin Prlic (Fred Hutchinson Cancer Center, USA) Immune cell communication in healthy and inflamed human tissues |
| 16:40-17:10 | Eui-Cheol Shin (Korea Virus Research Institute / KAIST, Korea) TCR signals counteract IL-15-induced, NK-like activation of memory CD8+ T cells |
| 17:10-17:40 | Ondřej Štěpánek (Institute of Molecular Genetics of the Czech Academy of Sciences, Czech Republic) Early activation and fate commitment in T cells |
| Session 6: Novel Strategies for Vaccines and Antivirals / Chair: Min-Suk Song, Hui-Ling Yen |
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| 09:30-10:10 | Adolfo Garcia-Sastre (Icahn School of Medicine at Mount Sinai, USA) A COVID-19 vaccine based on a Newcastle disease virus vector |
| 10:10-10:40 | Man-Seong Park (Korea University, Korea) Preparing better vaccines against influenza viruses |
| 10:40-11:10 | Hui-Ling Yen (The University of Hong Kong, Hong Kong) Antibodies against influenza virus neuraminidase |
| 11:10-11:40 | Min-Suk Song (Chungbuk National University, Korea) Capless Self-amplifying mRNA Vaccine Induces Robust Immune Response Against Highly Pathogenic Avian Influenza 2.3.4.4 H5 Virus |
Invited Speakers
Plenary Speakers
Invited Speakers
Biography
Yoshihiro Kawaoka, DVM, PhD
National Center for Global Health and Medicine – Director
University of Tokyo – Project Professor
University of Wisconsin-Madison – Professor
After receiving his DVM degree from the Ministry of Agriculture and Fishery, Japan and his PhD degree from Hokkaido University, Professor Yoshihiro Kawaoka began his career as a postdoctoral fellow at St. Jude Children’s Research Hospital. He became a professor at the University of Wisconsin-Madison in 1997 and at the University of Tokyo in 1999. He established a technique that allows the generation of ‘designer’ influenza viruses. This technology is used to update the influenza vaccine FluMist® and to generate bird influenza vaccines. Dr. Kawaoka’s group worked in Sierra Leone during the 2014–2016 Ebola outbreak and worked with Ebola survivors. In February 2020, he began research on SARS-CoV-2 to understand how the virus causes severe disease and to develop vaccines. In recognition of his achievements, Dr. Kawaoka was awarded the Robert Koch Award in 2006; he was elected as an international member of the United States National Academy of Sciences in 2013, and as a fellow of the National Academy of Inventors in 2023.
Biography
Chair Professor
State Key Laboratory of Emerging Infectious Diseases, School of Public Health, The University of Hong Kong
yguan@hku.hk
Professor Yi Guan is the Director of the State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong. His research focuses on the ecology, evolution and pathogenesis of influenza and other emerging respiratory viruses. Over the past decade, his research team has made ground-breaking and distinguished contributions to research in virology and to the control of emerging infectious diseases in China and the world. His contribution to the field is reflected in his publication record of over 350 peer-reviewed articles with ~60,000 citations, and an h-index of 115.
Beginning in Year 2000, Professor Guan initiated and organized a systematic influenza surveillance network, in human, swine, poultry and migratory bird populations, in Southern China. Through this surveillance over 100,000 samples from poultry are collected each year, representing the single largest continuous and systematic sampling of these disease reservoirs. Along with providing the majority of World Health Organization recommended H5N1 and H9N2 pre-pandemic vaccine strains, the information from this surveillance program has provided the most comprehensive understanding of the ecology, evolution and dissemination of avian influenza viruses influenza viruses with pandemic potential worldwide.
He also initiated the SARS etiological investigation in Guangdong that resulted in the Department of Microbiology at HKU being the first research team to identify this emerging coronavirus and was the first to identify the virus in wild animal markets Guangdong showing this to be the interface for zoonotic transmission to humans. He subsequently organized and led the nationally coordinated investigation in China to determine the zoonotic source of SARS coronavirus, and advised the Chinese Government on control measures to successfully avert a second SARS outbreak in early 2004 in Guangdong.
His contributions on MERS have revealed the prevalence and evolution of the MERS coronavirus in its animal reservoir, which led to the human outbreaks in Korea and Saudi Arabia; and this work has identified a new coronavirus species co-circulating with the MERS coronavirus in camels. Recently during the COVID-19 outbreak, his team has found pangolin to be one of the hosts for SARS-like coronaviruses and international trading/smuggling could be a way for virus emergence from the zoonotic source.
Professor Yi Guan has consistently been ranked as a highly cited researcher (2014-2019) and has been ranked 11th in the world in the field of microbiology (Thomson 2014). His annual personal ranking has been 5th and 4th in the world, respectively, in the field of avian influenza and H1N1 influenza research, 2005 and 2009 (Thomson Institute of Scientific Information ISI Ranking). He has obtained substantial grant funding from the NIH of the USA, the Welcome Trust fund and the WHO as well as from local government sources and private foundations. “Time” magazine of the USA has twice featured him, first as one of 18 “Global Health Heroes” and later as an “Asian Hero”.
Biography
Professor and Chair
Cleveland Clinic
jungj@ccf.org
Prof. Jung is currently Betsy B. deWindt Professor, Chair of Cancer Biology Department, Director of Infection Biology Program, and Director of Global Center for Pathogen and Human Health Research at Lerner Research I nstitute, Cleveland Clinic.
Originally from South Korea, Prof. Jung began his career as a fellow and later a tenured professor of Microbiology and Molecular Genetic at Harvard Medical School and served as Chair of the Tumor Virology Division (1989-2007). Dr. Jung transitioned to University of Southern California, assuming the roles of Fletcher Jones Foundation Endowed Chair, Distinguished Professor, Chair of the Molecular Microbiology and Immunology Department, and Director of the USC Institute of Emerging Pathogens and Immune Diseases at the Keck School of Medicine (2007-2020).
Prof. Jung has been awarded South Korea’s 2012 Ho-Am Prize in Medicine. He is Fellow of American Academy of Microbiology and Fellow of American Association for the Advancement of Science. He was a recipient of the Scholar Award of the Leukemia and Lymphoma Society of America, Howard T. Ricketts Lecture Award, Dr. Windsor and Mary Cutting Lecture Award, and the National Institute of Cancer Outstanding Investigator Award.
He received the B.S. degree (1982) and M.S. degree (1984) from the department of the Food Science at Seoul National University, Korea. He then received Ph.D. degree from the department of Microbiology at University of California-Davis in 1989.
Biography
Kanta Subbarao
Professor
Laval University, Quebec City, Canada and University of Melbourne, Melbourne, Australia
kanta.subbarao@unimelb.edu.au
Prof Kanta SUBBARAO is a Canada Excellence Research Chair Professor in the Department of Microbiology and Immunology, Laval University, Quebec, Canada and an honorary professor in the Department of Microbiology and Immunology at the University of Melbourne at the Peter Doherty Institute in Melbourne, Australia. She is a physician scientist whose research is focused on newly emerging and re-emerging viral diseases of global importance including pandemic and seasonal influenza and corona- viruses.
Prof Subbarao received her medical degree (MBBS) from Christian Medical College, Vellore (University of Madras), India followed by residency training in pediatrics at Saint Louis University and fellowship in pediatric infectious diseases at the University of Oklahoma. She also received an MPH degree from the School of Public Health at the University of Oklahoma. Following this, she was a postdoctoral fellow in the Laboratory of Infectious Diseases at the National Institutes of Health.
Prof Subbarao was Chief of the Molecular Genetics Section of the Influenza Branch at the US Centers for Disease Control (1997-2002), Chief of the Emerging Viruses Section of the Laboratory of Infectious Diseases at the National Institutes of Health (2002-2016) and Director of the WHO Collaborating Centre for Influenza in Melbourne from 2016-2024. She held honorary academic appointments from 1996 till the present.
Prof Subbarao is a member of the WHO technical advisory group on COVID-19 vaccines and chaired the committee from 2021-2024. She has served as a member of WHO advisory panels on seasonal and pandemic influenza vaccines and the Australian National Influenza Surveillance Committee.
She is a Fellow of the Australian Academy of Health and Medical Sciences, the American Academy of Microbiology and the Infectious Diseases Society of America. She is on the Editorial Boards of PLoS Pathogens, Journal of Virology, Cell Host and Microbe and Med.
Biography
Dr. García-Sastre is Professor in the Departments of Microbiology, of Medicine, of Pathology, Molecular and Cell-Based Medicine, and in the Tisch Cancer Center at Icahn School of Medicine Mount Sinai (ISMMS) in New York. He is also Director of the Global Health and Emerging Pathogens Institute at ISMMS, and Principal Investigator for the Center for Research on Influenza Pathogenesis and Transmission (CRIPT), a NIAID Center of Excellence for Influenza Research and Response (CEIRR). For the past 30 years, his research interest has been focused on the molecular biology, virus-host interactions, innate immunity and pathogenesis of influenza viruses and several other RNA viruses, as well as on the development of new vaccines and antivirals. He has more than 700 peer-reviewed publications in these areas of research. He has been President of the International Society for Vaccines in 2014-2015. He is Editor for the scientific journal PLoS Pathogens , Editor-in-Chief for Current Opinion in Virology, and has been editor for Journal of Experimental Medicine, Journal of Virology and Virus Research. In 2017, he has been elected a fellow of the Royal Academy of Pharmacy in Spain. In 2019, he was recognized with a Honorary Doctor Degree from the University of Burgos, Spain. Also in 2019, he was elected a member of the National Academy of Sciences and of the National Academy of Inventors.
Abstract
Addressing the threat of emerging viral infections
Yoshihiro Kawaoka, DVM, PhD
National Center for Global Health and Medicine
University of Tokyo
University of Wisconsin-Madison
Every year, influenza epidemics occur, causing increased morbidity and mortality, particularly in vulnerable populations, such as the very young and very old. In addition, pandemics, such has the 1918 pandemic, occasionally occur. Consequently, influenza has an enormous impact on the global economy. In December 2019 in China, SARS-CoV-2 emerged and spread globally, causing the fifth pandemic since the 1918 pandemic. I will discuss our recent research on these viruses.
Abstract
Origin and Emerging of COVID-19
Tommy Tsan Yuk Lam, Yi Guan
State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong
School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong
Understanding the origin of COVID-19, like any pandemic, is crucial to inform prevention of the emergence of similar pathogens in humans. Virus emergence occurred via different host pathways have marked their footprints in the virus genomes, and are associated with the virus-host interaction and ecology. We reviewed the emergence pathways of human coronaviruses including SARS-CoV-1 & 2, MERS-CoV, NL63, 229E, OC43 and HKU1, by including viruses detected in our wildlife virome. Host jump events from bats as natural reservoirs to putative intermediate hosts were observed. Virus genomic features in the host switching process including the GC content and furin cleavage sites were investigated. The findings suggest that animals other than bats could have played an intermediary role in facilitating the emergence of coronaviruses including SARS-CoV-2 in humans. More coronavirus surveillance and studies in animals in the future would provide useful information to delineate the emergence pathway of SARS-CoV-2 and inform evidence-based disease prevention and control.
Abstract
Intervention Approach of Emerging Viruses
Jae Ung Jung
Cancer Biology Department, Infection Biology Program, and Global Center for Pathogen & Human Health, Cleveland Clinic, OH, USA
Severe fever with thrombocytopenia virus (SFTSV) initiates viral mRNA synthesis through a unique “cap-snatching” mechanism. During this process, the C-terminal Cap-binding domain (CBD) of the RNA-dependent RNA polymerase (RdRp) recognizes the 5’ end of host cell mRNAs. Subsequently, the N-terminal endonuclease (EndoN) of the RdRp cleaves the recognized mRNA, generating capped mRNA fragments that serve as primers for viral mRNA synthesis. This mechanism shares similarities with other cap-snatching viral EndoNs, such as influenza virus PA, but also exhibits distinct characteristics. As the cap-snatching mechanism is indispensable for SFTSV replication, the CBD and EndoN are outstanding drug targets to inhibit SFTSV replication.
SARS-CoV-2 possesses multiple nonstructural proteins (Nsps) involved in various aspects of viral replication. Among these, Nsp14 features an amino-terminal 3′ to 5′ exoribonuclease (ExoN) and a carboxyl-terminal guanine-N7-methyltransferase activity (N7-MTase). The N-terminal ExoN domain is predicted to provide proofreading activity, enabling the removal of mismatched nucleotides introduced by the viral RNA-dependent RNA polymerase (RdRp). Given the large viral genome of coronaviruses, the proofreading activity of the ExoN domain is crucial for maintaining a high level of replication fidelity. Unlike the typical replication fidelity (103–105) of RNA viruses, the low mutation rate (106–107) of SARS-CoV is attributed to the ExoN activity, underscoring the essential role of Nsp14 ExoN activity in the viral lifecycle. SARS-CoV-1/2 Nsp14 forms a protein complex with Nsp10, a zinc-binding protein. Importantly, mutations in Nsp10 that disrupt the Nsp14−Nsp10 interaction result in a lethal phenotype in SARS-CoV, highlighting the crucial role of the Nsp10-Nsp14 interaction in the viral lifecycle.
My presentation focuses on identifying lead candidates for SFTSV EndoN and CBD inhibitors, as well as SARS-CoV-2 ExoN inhibitors, and evaluating their antiviral therapeutic efficacy in cell-based studies and animal models.
Abstract
Zoonotic, Pandemic and Endemic Coronaviruses
Kanta Subbarao
Laval University and University of Melbourne, Quebec City, Canada and Melbourne, Australia
Influenza A viruses and coronavirus infections in humans occur in three scenarios: zoonotic, seasonal or pandemic. To explore these scenarios, our research focuses on the biology of virus infection and airborne spread of coronaviruses. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and endemic human coronaviruses primarily infect the respiratory tract. We have established cell culture models that represent different parts of the human respiratory tract, including nasal epithelial cells, large-airway and small-airway epithelial cells, and embryonic stem cell-derived type II alveolar cells for the study of SARS-CoV-2 and endemic human coronaviruses. In addition, because other organ systems are involved in COVID-19, we established human stem cell-derived cardiac, kidney and placental cultures to explore molecular mechanisms of SARS-CoV-2 biology. We have established methods to recover infectious SARS-CoV-2 from air samples that will provide insights into airborne transmission. Our data on SARS-CoV-2 and endemic human coronaviruses provide novel insights into virus biology, rational drug combinations for treatment and airborne spread.
Abstract
A COVID-19 vaccine based on a Newcastle disease virus vector
Adolfo García-Sastre1
1Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
SARS-CoV-2 vaccines were developed and deployed in less than one year since the origin of the COVID-19 pandemic and have clearly reduced the percentage of severe infections in countries where they have been widely used. However, many developing countries have problems to afford the purchase and/or distribution of many of the approved vaccines. In addition, most of the widely used current vaccines provide with limited mucosal immunity to appropriately prevent infections. New efficacious and safe SARS-CoV-2 vaccines that could be manufactured locally in developing countries, that would not require ultra-congelation and that would induce infection-preventing mucosal immunity are desirable. We have been working in the development of such a vaccine based on a Newcastle disease virus (NDV) vector. This avian virus is widely used as live and inactivated vaccine in poultry against Newcastle disease, a potentially devastating avian disease. NDV inoculation in mammals results in abortive infection due to the induction of a robust local innate immune response that inhibits further virus replication while potentiating the induction of adaptive immune responses. NDV vaccines are manufactured using the same technology as most of the influenza virus vaccines, making it possible its production in most developing countries. We have generated NDV-based vaccines expressing a stabilized version of the S protein of SARS-CoV-2. These vaccines are stable at 2 degrees and provide protection against SARS-CoV-2 and its variants in animal models. NDV-based vaccines not only express the vaccine antigen in infected cells, but also incorporate the antigen into the virion, making it possible the use of either live or inactivated versions of the vaccine. Results from clinical trials demonstrated lack of severe adverse events and very mild reactogenicity, as well as the induction of a robust T cell and neutralizing antibody response against SARS-CoV-2. Additional clinical trials have been initiated using live intranasal administration which has the potential to generate a more potent mucosal immunity for prevention of not only disease but also asymptomatic infections and transmission.
Biography
Kyun-Hwan Kim
Professor
Sungkyunkwan University
khkim10@skku.edu
Prof. Kyun-Hwan Kim is a molecular virologist, currently a Professor of Precision Medicine at Sungkyunkwan University Medical School. He initially trained in Korea, obtaining a BS/MS from the Seoul National University and a Ph.D. at the Yonsei University, followed by postdoctoral studies at Brown University. He returned to Korea in 2005 to establish a Virology research laboratory at the Konkuk University in Seoul. He moved to Sungkyunkwan University in Mar 2020.
The Kyun-Hwan Kim’s lab works in the fields of hepatitis B virus, influenza virus, corona virus, and virus-related diseases, attempting to decipher the molecular and cellular mechanisms that control viral replication, life-cycle, and virus-induced pathogenesis. Current interests and investigations include the viral evasion against host immune systems, drug resistance, and development of antivirals.
Biography
Sanghyun Lee
Assistant Professor
Brown University
Sanghyun_Lee@brown.edu
Dr. Sanghyun Lee has dedicated his scientific career to dissecting host-virus interactions at molecular and physiological levels, aiming to understand how these interactions contribute to viral pathogenesis. He earned his Ph.D. from Seoul National University in Korea, focusing on viral non-coding RNAs and their role in the virulence of human cytomegalovirus. Following his doctoral training, he pursued a postdoctoral training in Skip Virgin lab and Megan Baldridge lab at Washington University in St. Louis, where he investigated cellular tropism for norovirus and interferon-lambda mediated immune control in the intestine. In 2020, Dr. Lee established his independent research program at Brown University, where his group has been actively exploring novel host-virus interactions and seeking to develop vaccines and therapeutics for enteric viruses and coronaviruses.
Biography
SangJoon Lee
Assistant Professor
Department of Biological Science, UNIST, Republic of Korea
sangjoon.lee@unist.ac.kr
Professor SangJoon Lee commenced his research career during his doctoral studies at the University of Tsukuba (Japan), investigating innate immunity against influenza infection. He subsequently undertook postdoctoral fellowships at the University of Tsukuba and St. Jude Children’s Research Hospital (USA), focusing on innate immunity against various viral infections and a form of cell death known as PANoptosis.
In 2022, Professor Lee assumed the role of Assistant Professor in the Department of Biological Science at the Ulsan National Institute of Science and Technology (UNIST), where his research has centered on inflammasomes and inflammatory cell death in the context of innate immunity, infectious diseases, inflammatory disorders, and cancer.
Throughout his career, Professor Lee has been the recipient of numerous prestigious awards and honors, including the HBP Fellow Award in 2013 (University of Tsukuba), the Outstanding Research Award (University of Tsukuba) in 2019, the Yuhan Innovation Program Award (Yuhan Corporation) in 2022, and appointment as Director of the UNIST Pandemic Research Center in 2023 (The Circle Foundation).
Biography
Jinjong Myoung
Professor
Korea Zoonosis Research Institute, Jeonbuk National University
Jinjong.Myoung@jbnu.ac.kr
Prof. Myoung is currently a Professor at Jeonbuk National University, Jeonju, Korea. His research field of interest is molecular virology and vaccines against coronaviruses.
- He completed his Bachelor’s and Master’s degrees at the Department of Microbiology, Seoul National University, before advancing to the Integrated Program in Life Sciences (IGP) for his PhD, where he focused on TMEV-IDD, a mouse model of Multiple Sclerosis
- Subsequently, he undertook a postdoctoral fellowship in Don Ganem’s Lab at UCSF, where he conducted significant research on the mechanisms of B cell infection and oncogenesis by KSHV
- In 2011, he transitioned to the Novartis Institutes for Biomedical Research with Don Ganem, who served as Vice President at the Division of Infectious Diseases
- Following his postdoctoral training, he joined the Korea Zoonosis Research Institute at Jeonbuk National University, where he has progressed through the ranks from Assistant to Associate to Full Professor
- The overarching theme of his research history has been host-pathogen interactions, with a specific emphasis on immune cell responses and the control of viral infections. He is currently expanding his scientific horizons to emerging viruses, such as Zika virus, MERS-CoV and SARS-CoV-2
Biography
Yong Taik Lim
Professor
Sungkyunkwan University
yongtaik@skku.edu
Prof. LIM is currently a Professor at the Department of Nano Engineering and SKKU Advanced Institute of Nanotechnology in Sungkyunkwan University (SKKU), Suwon, Korea. His research field of interest is Immuno-Bio-Engineering for Cancer Immunotherapy and Infectious Disease. He is developing designer biopharmaceuticals for cancer immunotherapy and vaccine adjuvants for infectious disease.
After he received his Ph.D. degree at the Department of Chemical and Biomolecular Engineering in the Korea Advanced Institute of Science and Technology (KAIST) in 2002, he joined John V. Franginoni’s laboratory at Harvard Medical School as a postdoctoral research fellow. He also worked about 5 years at the two Korea government-supported research institutes (ETRI and KRIBB) as an alternative military service. He started professorship at Chungnam National University in 2009 and moved to Sungkyunkwan University in 2014.
He received the B.S. degree from the department of the Chemical Engineering at the Sogang University, Korea in 1996. He then received the M.S. degree from the department of Chemical and Biomolecular Engineering at the Korea Advanced Institute of Science and Technology (KAIST) in 1998 and Ph.D. at KAIST in 2002.
Biography
Hye-Ra Lee
Professor
Department of Biotechnology and Bioinformatics, Korea University, South Korea
leehr@korea.ac.kr
Prof. Hye-Ra Lee is a professor of the Department of Biotechnology & Bioinformatics at Korea University. Before taking her current position, she served as an Assistant Professor of Research at the University of Southern California, USA, a role she assumed after completing her post-doc activities at the same institution. She also serves as a member of the editorial board of Journal of Virology and the Journal of Microbiology, and as an associated editor of Frontier in Microbiology. Her research projects are centered on tumors associated with gamma-2 herpesviruses. Specifically, she has elucidated immune evasion tactics mediated by Kaposi’s sarcoma-associated herpesviruses (KSHV) against the host’s immune system and the molecular mechanisms of tumors induced by the KSHV. Ultimately, from the perspective of basic science, she is dedicated to developing new anti-cancer agents as well as anti-viral agents. Her current research explores how KSHV and flaviviridae virus deregulate the functions of lymphatic endothelial cells, contributing to virus-associated pathogenesis. Furthermore, she focuses on development of multivalent vaccines targeting these viruses.
Biography
Professor Young Ki Choi, DVM, Ph.D
Professor, College of Medicine, Chungbuk National University, Korea
Managing Director, Korea Virus Research Institute KVRI), Institute for Basic Science (IBS), Korea
Director, Centre for Emerging and Re-emerging Viral Diseases (KVRI), Korea
E-mail: choiki55@ibs.re.kr
Tel (office): +82-42-878 8350
Professor Choi obtained his B.S. and M.S. from the College of Veterinary Sciences at Chungnam National University and received a Ph.D. in Virology at the University of Minnesota. During his post-doc fellowship under the mentorship of Dr. Robert Webster at St. Jude Children’s Research Hospital, he experienced many laboratory and field studies on highly pathogenic zoonotic viral diseases. He has served as a professor at Chungbuk National University’s College of Medicine, where he researched the pathogenic mechanisms by which viruses infect hosts and vaccine development. His recent studies on SFTSV and COVID-19 have garnered much attention at home and abroad, which include establishing the animal models of virus infections and transmissions. From July 2021, he has been conducting research on Emerging and re-emerging viral diseases as the managing director at the Korea Virus Research Institute in the Institute of Basic Science (IBS).
Education / Career
2021.07-present. Managing Director, Korea Virus Research Institute. Institute for Basic Science (IBS), Daejeon 34126, Republic of Korea
2024.09- 2023.10. Professor, Chungbuk National University, Korea
2003-2004.08. Post-doctoral fellow, St. Jude Children’s Research Hospital, USA
Ph.D. (2002). University of Minnesota, USA.
Bs, Master. (1999) College of Veterinary Medicine, Chung-Nam National University, South Korea.
Selected Publications List
- Ferrets animal model of severe fever with thrombocytopenia syndrome phlebovirus for human lethal infection and pathogenesis. Park SJ, et al. Nature Microbiol, 4(3):438-446, 2019.
- Cross-genotype protection of live-attenuated vaccine candidate for severe fever with thrombocytopenia syndrome virus in a ferret model. Yu KM, et al. Proc Natl Acad Sci U S A, Vol 116, no 52 26, 26900-26908, 2019
- Development of an SFTSV DNA vaccine that confers complete protection against lethal infection in ferrets. Kwak JE, et al. Nature Commun, 23;10(1):3836, doi:
- Infection and Rapid Transmission of SARS-CoV-2 in Ferrets. Kim YI, et al. Cell Host Microbe, 5, pii: S1931-3128(20)30187-6, 202010.1038/s41467-019-11815-4, 2019.
- A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein. Kim C, et al. Nat Commun, 12;12(1):288, doi: 10.1038/s41467-020-20602-5, 2021.
- Single-cell transcriptome of bronchoalveolar lavage fluid reveals sequential change of macrophages during SARS-CoV-2 infection in ferrets. Lee JS, Koh JY, Yi K, Kim YI, et al, Nat Commun. 2021 Jul 27;12(1):4567. doi: 10.1038/s41467-021-24807-0.
- Age-dependent pathogenic characteristics of SARS-CoV-2 infection in ferrets. Kim YI, Yu KM, Koh JY, et al, Nat Commun. 2022 Jan 10;13(1):21. doi: 10.1038/s41467-021-27717-3.
Biography
professor
State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
zhengaihua@ioz.ac.cn
Prof. Aihua Zheng is currently a professor at the State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. His research focuses on transmission mechanism of arbovirus and the development of blocking strategies.
His lab works on mosquito- and tick- borne viruses, such as dengue, Zika and SFTSV. Research topics includes the molecular mechanisms of arbovirus infection and cross-species transmission, as well as the ecological mechanism of virus dispersal in nature. As the corresponding author, he has published 18 papers in PNAS, Nature Communications, Emerging Infectious Diseases, Plos Pathogens, Emerging Microbe & Infection, Signal Transduction & Targeted Therapy and other journals, and 6 patents have been licensed. He is the director of the Insect Comparative Immunity and Interaction Committee of the Entomological Society of China, and a member of the International Working Committee of the Entomological Society of China.
He received the B.S. degree from the Department of Biochemistry and Molecular Biology in Nankai University, China in 2001. He then received the Ph.D degree from Prof. Hongkui Deng’s lab in the Department of Cell Biology at the Beijing University in China in 2007. He did his post-doc training in Prof. Margaret Kielian’s lab in Albert Einstein College of Medicine in Bronx, New York, working on the fusion and exit of dengue virus.
Biography
Nam-Hyuk Cho
Professor
Seoul National University College of Medicine
chonh@snu.ac.kr
Dr. Nam-Hyuk Cho has a longstanding interest in host-pathogen interactions, particularly in emerging human pathogens. He received the B.S. degree from the department of the genetic engineering at the Korea University in 1996. He then received the M.S. degree from the graduate school of biotechnology at the Korea University in 1998 and Ph.D. degree from the department of Microbiology and Immunology at the Seoul National University College of Medicine in 2001.
He is currently a professor in the Department of Microbiology and Immunology at Seoul National University College of Medicine, Seoul, South Korea. Dr. Cho began studying immune responses and immunopathogenesis during the infection of Orientia tsutsugamushi, the causative agent of scrub typhus, during his Ph.D. training at Seoul National University. He expanded his research areas to virology while undergoing postdoctoral training at Harvard Medical School. Dr. Cho has a broad background in cellular immunology, molecular biology, microbiology, and virology. He has collaborated with clinicians in several Korean hospitals to study the immunological pathogenesis of several endemic and new emerging infectious diseases, including scrub typhus, severe fever with thrombocytopenia syndrome (SFTS), and emerging coronavirus infections.
Dr. Cho’s team has been exploring potential antigens for vaccine development through animal model studies and clinical research on scrub typhus. Additionally, their research extends to virus-host cell interactions, particularly with emerging viral pathogens such as SFTSV, MERS-CoV, and SARS-CoV-2. By elucidating the fundamental mechanisms utilized by these emerging human pathogens, his work aims not only to contribute to effective strategies against severe infections but also to offer insights into the evolutionary development of our immune system. The ultimate objective of Dr. Cho’s research is the artificial engineering of immune structures through immunoarchitectonic approach, which aims to regulate our immune response to a variety of human diseases, including infections and cancers.
Biography
Meehyein Kim
Doctor
Korea Research Institute of Chemical Technology
mkim@krict.re.kr
Meehyein Kim received her Ph.D. in Chemistry in 2000 from Korea Advanced Institute of Science and Technology (KAIST). Since 2010, she has worked at the antiviral research group as a principal researcher in Korea Research Institute of Chemical Technology (KRICT). M. Kim has interests in discovery of antiviral compounds against influenza virus and coronavirus through investigation of their mode-of-action.
Representative publications (for recent 3 years):
- Inhibition of endocytic uptake of severe acute respiratory syndrome coronavirus 2 and endo-lysosomal acidification by diphenoxylate, Antimicrobial Agents and Chemotherapy (2024), In press
- A dual inhibitor of PIP5K1C and PIKfyve prevents the cell entry of SARS-CoV-2, Experimental and Molecular Medicine (2024), Accepted
- Discovery of antiviral SARS-CoV-2 main protease inhibitors by structure-guided hit-to-lead optimization of carmofur. European Journal of Medicinal Chemistry (2023), 260:115720
- Intracellular Dynamics-Resolved Label-Free Scattering Reveals Real-Time Metabolism of Single Bacteria, Nano Letters (2023), 23: 8225-8232
- Identification of broad-spectrum neutralizing antibodies against influenza A virus and evaluation of their prophylactic efficacy in mice, Antiviral Research (2023), 213:105591
- Evaluation of Antiviral Activity of Gemcitabine Derivatives against Influenza Virus and Severe Acute Respiratory Syndrome Coronavirus 2, ACS Infectious Diseases (2023), 9:1033
- Label-free detection and discrimination of respiratory pathogens based on electrochemical synthesis of biomaterials-mediated plasmonic composites and machine learning analysis, Biosensors & Bioelectronics (2023), 227:115178
- Repurposing of cyclophilin A inhibitors as broad-spectrum antiviral agents, Drug Discovery Today (2022), 27:1895
- Generation of human tonsil epithelial organoids as an ex vivo model for SARS-CoV-2 infection, Biomaterials (2022), 283:121460
- Antiviral activity of lambda‑carrageenan against influenza viruses and severe acute respiratory syndrome coronavirus 2, Scientific Reports (2021), 11:821 (Top 100 microbiology Scientific Reports papers in 2021)
- Determination of the vRNA and cRNA promoter activity by M segment-specific non-coding nucleotides of influenza A virus, RNA Biology (2021), 18:785-795
Biography
Je-Min Choi
Professor
Hanyang University
jeminchoi@hanyang.ac.kr
Dr. Je-Min Choi is a T-cell immunologist and a tenured professor at Hanyang University in Korea. He is a member of the Young-Korean Academy of Science and Technology (Y-KAST). Dr. Choi’s research career started during his master’s degree when he explored the antioxidant function of Neohesperidin dihydrochalcone against cellular stress and aging. During his Ph.D., he changed his research field to immunology and focused on studying CTLA-4 signaling in T cells and its potential to modulate inflammation in allergic asthma and autoimmune arthritis using cell-penetrating peptides. His postdoctoral training at Yale University involved studying Foxp3 transduction in T cells for immune modulation and investigating PPARγ in T cell response. Since he started his independent laboratory (Cellular Immunology Lab) at the Department of Life Science at Hanyang University in 2010, he has been at the forefront of developing macromolecular delivery peptides (dNP2, AP) in T cells over the tissue barrier, such as BBB (Blood-Brain Barrier), and skin tissue for efficient immune modulation. He also investigated the role of PPARγ in CD4 T cells concerning follicular helper T cell/germinal center response in controlling antibody response and sex-different autoimmunity. From 2017 to 2019, he served as the department chair at Hanyang University. He currently leads the CNS center (Convergence research center of Next-generation life Sciences) at HY-IBB (Hanyang Institute of Bioscience and Biotechnology) serving as a Deputy director. Dr. Choi’s primary research interests revolve around studying bystander T cell functions in autoimmune disease, infection, and cancer, as well as developing immune modulatory drugs by increasing tissue resident Treg cells for autoimmune disease therapy. His research has opened new avenues for understanding the immune system and has the potential to revolutionize the treatment of autoimmune diseases and cancer.
Biography
Ross M. Kedl
Professor
University of Colorado Anschutz Medical Campus
ross.kedl@cuanschutz.edu
Ross Kedl received his PhD in 1997 in Pathobiology at the University of Minnesota in the lab of Matthew Mescher. He then did his postdoctoral fellowship with HHMI investigators Pippa Marrack and John Kappler at National Jewish Health in Denver, CO. After his postdoctoral training, he initially went to 3M Pharmaceuticals to work in their small molecule immune response modifier program. While there, he became invested in developing novel vaccine adjuvants and vaccine technology. He returned to the academic sector in 2004 to the University of Colorado School of Medicine where he continues to pursue a better understanding of the adjuvant-elicited stimuli and signals which best initiate T cell activation and expansion. Experimentally his lab has demonstrated a number of ways of using vaccine adjuvants that can produce T cell expansion, effector function, and memory generation on par with that observed from a natural infection. Dr. Kedl’s lab has helped pioneer the idea that vaccine adjuvant-elicited T cell responses are counterintuitively motivated by immunological signals and pathways that are fundamentally different than those that motivate T cell responses against an active infection. They are using their understanding of the pathways and signals unique to vaccine-elicited cellular immunity to develop clinically relevant methods of therapeutic vaccination against diseases such as chronic infections and cancer.
Biography
Distinguished Scientist
Genentech
kimh101@gene.com
Dr. Kim is a Distinguished Scientist at Genentech in the USA, specializing in regulatory T cell biology and its crucial role in immune homeostasis.
She obtained her B.S. degree in Biology from Seoul National University in Korea and earned her PhD in Immunology from the Free University of Berlin in Germany in 2000. Following her PhD, Dr. Kim advanced her training in the United States, focusing on T cell development and immune regulation during her postdoctoral research at Memorial Sloan Kettering Cancer Center in New York City and the Dana-Farber Cancer Institute at Harvard Medical School in Boston.
Dr. Kim began her professional career as a Lead Scientist at the Dana-Farber Cancer Institute and served as a lecturer at Harvard Medical School from 2014-2022. In 2022, she joined Genentech as a Distinguished Scientist, where she now leads the Immune Tolerance program within the Immunology Discovery department.
Biography
Martin Prlic
Professor
Fred Hutchinson Cancer Research Center
mprlic@fredhutch.org
Prof. Prlic is currently a Professor at the Fred Hutchinson Cancer Research Center, Seattle, Washington. His research is focused on defining the signals that regulate immune responses, particularly T cell responses, in healthy, inflamed and tumor tissues. As an overarching lab goal and strategy, the Prlic lab strives to define the environmental cues that guide activation, differentiation and maintenance of immune cell populations to learn how these cues could be manipulated for therapeutic purposes. The Prlic lab develops and applies different single-cell analysis strategies including single-cell RNAseq, high parameter flow cytometry and AbSeq (linking protein biomarker expression to accomplish this goal.
Prof. Prlic received the M.S. degree from the University of Salzburg, Austria in 1999. He then moved from Austria to the US for graduate school and received the Ph.D. degree from the University of Minnesota in 2004. After his Ph.D., he joined the laboratory of Michael Bevan at the University of Washington as a post-doctoral fellow for 5 years.
Dr. Prlic started his professional career as an Assistant Professor in the Vaccine and Infectious Disease Division at the Fred Hutchinson Cancer Research Center (2011), and was promoted to Professor in 2023. He has affiliate faculty appointments at the University of Washington with the Department of Immunology, and the Department of Global Health. He has been a member of the American Association of Immunologists (AAI) since 2011 and has served as a lecturer for the AAI Introductory Course in Immunology since 2016.
He has received various prestige awards such throughout his career such as the Leukemia and Lymphoma Society Special Fellow Award (2005), the “Theodor Korner Prize” from the Austrian government for outstanding scientific achievements (2008) and the NIH Director’s New Innovator Award (2012) from the National Institutes of Health.
Biography
Prof. Eui-Cheol Shin received his M.D. (1996) and Ph.D. (2001) from Yonsei University College of Medicine, Seoul, Republic of Korea, and his postdoctoral training from NIDDK, National Institutes of Health, Bethesda, Maryland, USA. Then he joined Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea in 2007, where he is currently a professor. He also serves as the director of the Center for Viral Immunology, Korea Virus Research Institute, Institute for Basic Science (IBS), Daejeon, Republic of Korea, since 2021. His laboratory performs researches on T cell responses in human viral disease and cancer. In particular, he currently focuses on ‘T cell-mediated immunopathogenesis’, ‘senescence of T cells’, ‘reinvigoration of exhausted T cells’, and ‘immune responses in SARS-CoV-2 infection and COVID-19’. Prof. Shin was elected as a member of The Korea Academy of Science and Technology and The National Academy of Medicine of Korea in 2019 and 2024, respectively.
Biography
Ondřej Štěpánek
Doctor
Institute of Molecular Genetics, Prague
Ondrej.stepanek@img.cas.cz
Dr. Stepanek is a senior group leader at the Institute of Molecular Genetics of the Czech Academy of Sciences in Prague, Czech Republic. His group investigates fundamental mechanisms of T-cell biology in the context of various disease models.
He started his professional career as a PhD student of Immunology at the Charles University in Prague (2007-2011). He performed his postdoctoral research with Prof. Ed Palmer at the University Hospital of Basel (2012-2016). In 2016, he established his independent Laboratory of Adaptive Immunity as a junior group leader. He was promoted to a senior group leader in 2023.
He was awarded various prestige international grants such as EMBO Installation Grant (2016-2021), two grants from the European Research Council (2019-2023 Starting Grant and 2025-2029 Consolidator Grant), and Promys from the Swiss National Science Foundation (2016-2020).
He received the BA. degree from the University of Economics in Prague in 2005, MSc. degree from the Charles University in Prague in 2007 (Department of Genetics and Microbiology), and PhD degree from the Charles University in Prague in 2011 (Department of Cell Biology).
Biography
Professor
Department of Microbiology, Korea University College of Medicine
ms0392@korea.ac.kr
Prof. Park is currently a Professor at Korea University College of Medicine, Seoul, Korea. His research field of interest is RNA viruses including influenza viruses, SARS-CoV-2, and hantaviruses.
He received a Ph.D. degree from the Korea University in 1999. He started his professional career as an instructor in the Department of Microbiology at the Icahn School of Medicine at Mount Sinai (2005-2007), New York, USA, and moved to Hallym University, Chuncheon, Korea in 2007, and then moved to Korea University in 2014 where he was later appointed as the chairman of the Department of Microbiology.
He is currently working on vaccine and anti-viral drug development of negative-strand RNA viruses.
Biography
Hui-Ling Yen
Associate Professor
School of Public Health, LKS Faculty of Medicine, The University of Hong Kong
hyen@hku.hk
Hui-Ling Yen is Associate Professor at the School of Public Health, LKS Faculty of Medicine, The University of Hong Kong. She received her Ph.D. in Epidemiological Sciences from The University of Michigan (2001-2005) and her postdoctoral training in influenza virology at St. Jude Children’s Research Hospital (2005-2008). Dr. Yen joined HKU in 2009 as a Research Assistant Professor and was promoted to Assistant Professor in 2012 and Associate Professor in 2018.
Dr. Yen’s research focuses on identifying factors that facilitate the spread of respiratory viruses using laboratory experiments and field studies, with the aim of finding effective interventions to break the “agent-host-environment interactions” critical for viral spread. She works with interdisciplinary research groups to study the relative significance of transmission modes that mediate viral spread within and between species. Her laboratory also investigates viral adaptation and virus-host interactions during host switching, and molecular changes that confer spread of antiviral resistant variants.
Dr. Yen has been listed as a “Highly Cited Researchers in Cross-Field” by Clarivate. She received the AXA Research Award in 2015, HKU Faculty of Medicine Outstanding Research Output Award in 2021 and 2023, and the HKU Rosie Young 90 Medal for Outstanding Young Woman Scholar in 2024. Dr. Yen is a committee member at the antiviral group of the International Society for Influenza and Other Respiratory Virus Diseases (ISIRV). She serves as an Associate Editor for Influenza and Other Respiratory Viruses and at the Editorial Board of Antiviral Research.
Biography
Min-Suk Song
Professor
Chungbuk National University
songminsuk@chungbuk.ac.kr
Min-Suk Song, Ph.D., is currently a Professor at the College of Medicine and Medical Research Institute at Chungbuk National University in Cheongju-si, Korea. He specializes in microbiology with a focus on the pathogenesis of influenza viruses and the development of vaccines for infectious diseases.
Dr. Song began his academic journey at Chungbuk National University, earning his B.S. in Biology in 2006 and an M.S. in Microbiology in 2008. His master’s thesis, titled “Ecology of H3 Avian influenza viruses in Korea and assessment of their pathogenic potentials,” paved the way for his continued research in virology. He achieved his Ph.D. in 2011 with a thesis on the “Investigation of Pathogenic Determinants of Influenza Viruses in Mammalian and Their Molecular Characterizations.”
Following his doctorate, Dr. Song served as a postdoctoral research associate at the same institution from 2011 to 2012. He expanded his research horizons internationally as a postdoctoral research associate at St. Jude Children’s Research Hospital in the United States from 2013 to 2014. Returning to Chungbuk National University, he progressed from Assistant Professor in 2014 to Associate Professor in 2018, and was appointed full Professor in October 2023.
Dr. Song is leading a groundbreaking project focusing on the development of vaccines for infectious diseases using a capless self-amplifying RNA vaccine platform devised by his team. This innovative approach highlights his commitment to advancing medical research and public health.
He has been recognized for his contributions to virology and microbiology with several awards, including the Best Poster Presentation Award at the Options for the Control of Influenza VI Conference in Toronto in 2007 and the Most Valuable Paper Award at the 2016 TEPIK International Influenza Symposium.
Dr. Song is an active member of several professional societies, including The Korean Society for Microbiology and Biotechnology, The Korean Society of Virology, the American Society of Virology, and the Microbiology Society. His research continues to impact the field, focusing on molecular characterizations and pathogenic determinants of influenza viruses.
Abstract
Viral escape mechanisms against IFN-induced host defense
Kyun-Hwan Kim
Department of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon 440-746, Republic of Korea
Interferons (IFNs) mediate direct antiviral activity. They play a crucial role in the early host immune response against viral infections. However, there are several evidence that virus can evade host immune systems. For example, IFN therapy for HBV infection is less effective than for other viral infections. Influenza A virus (IAV) and coronavirus have also developed some counteraction against the host immune systems.
To explore the cellular targets involved in the interplay between host defense and viral response, we performed proteome and transcriptome screening. Using LC-MS/MS, we identified proteins downregulated and upregulated by IFN treatment in HBV X protein (HBx)-stable and control cells. We found several IFN-stimulated genes downregulated by HBx, including TRIM22, which is known as an antiretroviral protein. We demonstrated that HBx suppresses the transcription of TRIM22 through a single CpG methylation in its 5’-UTR, which further reduces the IFN regulatory factor-1 binding affinity, thereby suppressing the IFN-stimulated induction of TRIM22.
IAV is an important pathogen that infects a large proportion of the world population. It is responsible for pandemic flu and the deadliest Influenza epidemic in the past. PB1-F2 protein that was discovered recently is a virulence factor that plays an important role in pathogenesis of influenza virus and involved in induction of death in patients infected with Influenza and secondary bacterial infection. However, the mechanisms involved in the virulence of PB1-F2 have not been clearly elucidated. we show that the 1918 PB1-F2 protein not only interferes with the mitochondria-dependent pathway of type I IFN signaling, but also acquired a novel IFN antagonist function by targeting the DEAD-box helicase DDX3, a key downstream mediator in antiviral interferon signaling, toward proteasome-dependent degradation.
In current study, we further show that PB1-F2 antagonize the IFN antiviral signaling through downregulation of IFN-inducible TRIM22 expression, which was known to have anti-influenza activity. Furthermore, TRIM22 was also reduced in tonsil organoids infected SARS-CoV-2.
Figure 1. Schematic illustration of viral escape from IFN-induced host defense.
- Won J, Kang HS, Kim NY, Dezhbord M, Marakkalage KG, Park S, Kim DS, Kim KH. J Virol,
- Park ES, Byun YH, Park S, et al., & Kim KH, EMBO J,
- Lim KH, Park ES, Kim DH, et al., & Kim KH, GUT,
Abstract
Intestinal immune modulation by norovirus
Sanghyun Lee
Department of Molecular Microbiology and Immunology, Brown University, Providence, RI. USA
Interferons (IFNs) and programmed cell death in intestinal epithelial cells play a pivotal role in the frontline defense against enteric viral infections. This study utilizes a murine norovirus (MNoV) infection model in mice to elucidate a crucial immune evasion strategy employed by the virus to globally suppress the IFN-λ response. Genetic investigations unveil a novel aspect of how intestinal epithelial cells sense norovirus infection in tuft cells, emphasizing the significance of bystander non-tuft enterocytes in IFN-λ responses. MNoV employs the secreted virokine NS1 to counteract the production of IFN-λ in bystander cells, achieving tissue-wide suppression of IFN-λ responses. Notably, the production of NS1 is contingent upon the activation of cellular apoptosis. During infection, MNoV activates the key apoptosis enzyme, caspase-3, resulting in the direct cleavage of the viral precursor protein NS1/2 and its release from cells. Genetic ablation or pharmaceutical inhibition of caspase-3 effectively inhibits MNoV infection in mice. We will explore the viral exploitation of the cellular programmed cell death pathway to evade IFN-λ immunity in the intestine.
Abstract
Discovery of inflammasome sensors in viral infections
SangJoon Lee
Department of Biological Science, UNIST, Ulsan 44919, Republic of Korea
Inflammasomes are important sentinels of innate immune defense, sensing pathogens and inducing cell death (pyroptosis) in infected cells. There are several inflammasome sensors that each detect and respond to a specific pathogen- or damage-associated molecular pattern (PAMP or DAMP), respectively. During human herpes simplex virus-1 (HSV1) infection, we found that AIM2 regulates the innate immune sensors Pyrin and ZBP1 to drive inflammatory signaling and a form of inflammatory cell death (PANoptosis) and provide host protection (Nature, 2021). We further identified integrated NLRP3, AIM2, NLRC4, Pyrin inflammasome activation and assembly drive PANoptosis (Cellular & Molecular Immunology, 2023, Trends in Immunology 2024). Regarding SARS-CoV-2, the cytosolic innate immune sensors that sense SARS-CoV-2 to initiate PANoptosis is largely unknown. Using genome-wide CRISPR/CAS9 knockout screening and RNAseq analyses from human patients, we identified ZBP1 as an innate immune sensor that drives PANoptosis during SARS-CoV-2 infection (Science Immunology, 2022). Overall, our results improve our fundamental understanding of innate immune responses and disease pathogenesis by identifying an innate immune sensor-dependent inflammasome and PANoptosis and by defining its contribution to the pathological and life-threatening inflammation.
- Inflammasome diversity: Exploring novel frontiers in the innate immune response. G. Yu, Y. Choi, and Lee* (*Correspondence). Trends in Immunology (IF: 21.09), March. 21. 2024.
- Integrated NLRP3, AIM2, NLRC4, Pyrin inflammasome activation and assembly drive PANoptosis. S. Oh, J. Lee, J. Oh, G. Yu, H. Ryu, D. Kim, and Lee* (*Correspondence). Cellular & Molecular Immunology (IF: 24.1) Nov. 27, 2023.
- ZBP1-dependent inflammatory cell death, PANoptosis, and cytokine storm disrupt IFN therapeutic efficacy during coronavirus infection. R. Karki*, Lee*, R. Mall, N. Pandian, Y. Wang, B.R. Sharma, RKS. Malireddi, D. Yang, S. Trifkovic, JA. Steele, JP. Connelly, G. Vishwanath, M. Sasikala, DN. Reddy, P. Vogel, SM. Pruett-Miller, R. Webby, CB. Jonsson, and T.D. Kanneganti (*Equal contribution). Science Immunology (IF: 30.63), May 19 2022.
- AIM2 forms a complex with Pyrin and ZBP1 to drive PANoptosis and host defense. Lee, R. Karki, Y. Wang, L. Nguyen, R. Kalathur, and T.D. Kanneganti. Nature (IF: 69.5), Sept. 01, 2021.
Abstract
Reverse Genetics-based vaccines against SARS-CoV-2
Jinjong Myoung
Korea Zoonosis Research Institute, Jeonbuk National University, Jeonju 54896, Republic of Korea
Since its emergence in 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has initiated a global pandemic, transitioning into endemic status with significant public health challenges. The limitations of existing mRNA vaccines include decreased efficacy against variants such as Omicron, inadequate mucosal IgA induction, and cold-chain storage requirements. This study aimed to develop and assess a live attenuated SARS-CoV-2 vaccine designed to enhance both systemic and mucosal immune responses, targeting the virus at the initial point of entry. We engineered a live attenuated vaccine using a full-length infectious clone of SARS-CoV-2 with 3-4 specifically designed attenuating mutations. The vaccine underwent rigorous in vitro and in vivo attenuation confirmation and was extensively passaged in Vero E6 cells to ascertain safety. Immunogenicity was evaluated in hACE2-transgenic models receiving two intranasal doses. The vaccine induced robust production of mucosal IgA and systemic IgG. Following challenge with wild-type SARS-CoV-2, vaccinated subjects experienced no body weight loss or mortality, confirming the vaccine’s efficacy and safety. The engineered ‘Trojan Horse’ vaccine shows significant promise for effectively protecting against SARS-CoV-2, especially in high-risk populations. Its ability to induce strong mucosal and systemic immune responses may also prevent the emergence of more pathogenic viral variants. Further research is warranted to explore long-term immunity and potential for large-scale deployment.
Abstract
Engineered Nano-vaccines for Prolonged and Broad Protection against Heterologous Variants of SARS-CoV-2 and Influenza Virus
Yong Taik Lim
SKKU Advanced Institute of Nanotechnology (SAINT), Department of Nano Science and Technology, Department of Nano Engineering, School of Chemical Engineering, and Biomedical Institute for Convergence at SKKU, Sungkyunkwan University, Suwon, Republic of Korea. E-mail address: yongtaik@skku.edu
Demand for safe vaccines that ensure long-term and broad protection against multiple viral variants has dramatically increased after emergence of catastrophic infectious diseases such as COVID-19. Herein, we suggest two-types of novel engineered nanoadjuvants (SE(Trojan-TLR7/8a) and alum-Trojan-TLR7/8a) that evoke germinal centre (GC) B cells and polyfunctional T cells via multiscale kinetic immunomodulation through clinically approved platform (squalene nanoemulsion or alum)-mediated macroscopic control of vaccine delivery and the Trojan-TLR7/8a-enabled timely activation of antigen-presenting cells (APCs). Engineered nanoadjuvants enhance the migration of non-exhausted APCs into lymph nodes and elicit activation of follicular helper T cells and the generation of GC B cells and polyfunctional T cells. Engineered nanoadjuvants outperform current commercial vaccine adjuvants (Alum, AS03, or mRNA vaccines) and demonstrate cross-protection against diverse influenza and SARS-CoV-2 variants, ensuring 100% protection with a healthy state. Engineered nanoadjuvants also sustain a potent T cell response in an aged ferret model of SFTSV infection, demonstrating long-term and broad protective immunity against emerging pandemic and epidemic infectious viruses.
Abstract
EndMT by Intracellular Acetyl-CoA Flux Occurs the Disseminated Visceral Kaposi’s Sarcoma
Yeong Jun Kim1, Juhyeon Lim2, JunYoung Song1, Abhishek Kumar3, Shrute Kannappan4, Junjie Zhang5, Jin Hyun Nam6, Keong Kyu Kim4, Zsolt Toth3, Jae U Jung7, Hyungjin Eoh2, and Hye-Ra Lee1,8*
1Department of Biotechnology and Bioinformatics, College of Science and Technology, Korea University, Sejong, 30019, Republic of Korea
2Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA, 90033, USA
3Department of Oral Biology, University of Florida College of Dentistry, 1395 Center Drive, Gainesville, FL, 32610, USA
4Department of Precision Medicine, Sungkyunkwan University School of Medicine, Suwon, 2066, Republic of Korea
5The State Key Laboratory of Virology, Medical Research Institute, Wuhan University, Wuhan, China
6Division of Big Data Science, Korea University, Sejong, 30019, Republic of Korea
7Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
8Department of Lab Medicine, College of Medicine, Korea University, Seoul, 08308, Republic of Korea
Pyruvate kinase M2 (PKM2), a final rate-limiting enzyme of glycolysis, is recognized for its involvement in tumor initiation via aerobic glycolysis. However, its impact on acetyl-CoA regulation by pyruvate catabolism in cancer remains unclear. Here we found that interaction between KSHV vIRF3 and PKM2 has evolved as a unique strategy to control the metabolic switch of lymphatic endothelial cells (LECs), inducing disseminated visceral Kaposi’s Sarcoma (KS) in xenograft mouse models of recombinant KSHV-infected LECs. Mechanistically, the vIRF3-PKM2 interaction elevates intracellular acetyl-CoA levels by augmenting the enzymatic activity of PKM2, leading to the acetylation of SMAD2 and SMAD3, which contribute to the endothelial-mesenchymal transition (EndMT) of LECs. Notably, we discovered a vIRF3-derived short peptide as a potent and selective PKM2 antagonist, effectively regress the progression of KS. Collectively, these results suggest that the pivotal role of vIRF3 in KS malignancy causally links metabolic reprogramming of acetyl-CoA metabolism and cancer progression.
Abstract
Age-dependent different pathogenesis of viral diseases
Young-Il Kim, Choi YK
Korea Virus Research Institute, Institute for Basic Science (IBS), Korea
Host age is a critical intrinsic factor influencing the outcome of host-pathogen interactions, with specific pathogens exerting higher mortality in older hosts due to their unique clinical and ecological traits. During the SARS-CoV-2 pandemic, the seroprevalence of SARS-CoV-2 did not significantly differ among age groups in healthy individuals. However, persons aged 65 years or older exhibited markedly higher COVID-19 mortality compared to younger individuals. To elucidate the age-related manifestations of COVID-19, ferrets in three age groups were infected with SARS-CoV-2. Although SARS-CoV-2 was isolated from all ferrets regardless of age, aged ferrets demonstrated higher viral loads, prolonged nasal virus shedding, and more severe lung inflammatory cell infiltration and clinical symptoms compared to juvenile and young adult groups. Transcriptome analysis of aged ferret lungs revealed strong enrichment of gene sets related to type I interferon, activated T cells, and M1 macrophage responses, mirroring the gene expression profile of severe COVID-19 patients.
Similarly, the pathogenesis of influenza virus infections also exhibits age dependency. Elderly individuals often experience more severe influenza outcomes, including higher rates of hospitalization and mortality, compared to younger populations. A recent study identified dozens of key genes differentially expressed in kinetic, age-dependent, and cell type-specific manners. Aged immune cells exhibited altered inflammatory, memory, and chemotactic profiles, while aged endothelial cells demonstrated characteristics of reduced vascular wound healing and a prothrombotic state. Bulk RNA-seq generated a timeline of global transcriptional activity, showing increased expression of genes involved in inflammation and coagulation in aged lungs. These findings underscore the necessity of tailored therapeutic approaches and vaccination strategies for elderly populations.
Severe Fever with Thrombocytopenia Syndrome (SFTS), an emerging infectious disease caused by a novel phlebovirus, also shows age-dependent characteristics in its pathogenesis. Clinically, SFTS manifests as high fever, thrombocytopenia, leukocytopenia, gastrointestinal symptoms, and carries a high case-fatality rate. To understand the immunopathogenesis of SFTSV, we employed targeted proteomics and single-cell transcriptomics to analyze immune profiles in the blood of patients and virus-infected animal models. Our findings reveal a critical role for B cells in SFTSV pathogenesis, with distinct patient clusters exhibiting varying inflammatory cytokine levels correlated with disease severity. Furthermore, single-cell transcriptomics indicated significant B-cell expansion and subset alterations, particularly in fatal cases, highlighting the importance of B-cell dysregulation.
Collectively, this study elucidates the age-dependent pathogenic mechanisms of SARS-CoV-2 (a respiratory pathogen), influenza virus, and SFTSV (a systemic infection pathogen), with a specific focus on immune-cell dysfunction. These insights into the immune landscape of elderly patients offer valuable perspectives on potential therapeutic strategies targeting specific immune-cell modulation to mitigate the effects of viral infections.
Abstract
Natural circulation and spread of Severe fever with thrombocytopenia syndrome virus
Chaoyue Zhao, Xing Zhang, Aihua Zheng
State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
Severe fever with thrombocytopenia syndrome virus (SFTSV) is spreading rapidly in Asia. It is transmitted by Haemaphysalis longicornis, which has both parthenogenetically and sexually reproducing populations. Phylogeographic analysis suggested that the parthenogenetic population spread much faster than bisexual population because colonization is independent of sexual reproduction. Our results suggest that parthenogenetic H. longicornis, transported by migratory birds, play a major role in the rapid spread of SFTSV.
Wild amplifying host is necessary for the natural circulation of SFTSV. Our epidemiological field survey and experimental infection showed that hedgehogs were widely distributed, had heavy tick infestations, had high SFTSV seroprevalence and RNA prevalence, and produced robust but transitory viremias. Remarkably, SFTSV transmission cycle between hedgehogs and nymph/adult H. longicornis was easily accomplished under laboratory condition with 100% efficiency. Our study suggests that the hedgehogs are the major wildlife amplifying hosts of SFTSV.
Furthermore, we found the SFTSV natural foci in urban areas maintained by H. longicornis and hedgehogs, underscoring the need for urgent attention and enhanced surveillance measures.
Reference:
- Zhao C, et al. Hedgehogs as Amplifying Hosts of Severe Fever with Thrombocytopenia Syndrome Virus, China. Emerg Infect Dis. 2022 Dec;28(12):2491-2499.
- Zhang X, et al. Rapid Spread of Severe Fever with Thrombocytopenia Syndrome Virus by Parthenogenetic Asian Longhorned Ticks. Emerg Infect Dis. 2022 Feb;28(2):363-372.
Abstract
Hematopoietic dysregulation in Severe Fever with Thrombocytopenia Syndrome
Nam-Hyuk Cho
Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with a high fatality rate, closely associated with hematological abnormalities such as leukopenia, lymphopenia, and thrombocytopenia. The specific mechanisms behind these hematopoietic dysregulations and their role in SFTS pathogenesis have remained unclear. In this study, we reveal that the bone marrow microenvironment in SFTS patients undergoes significant reprogramming due to inflammation, leading to a skewing of hematopoietic stem and progenitor cells (HSPCs) towards the myeloid lineage. This reprogramming is characterized by an increase in CD14+CD16+ monocytes and IgG+ B cells. Using an IFNAR1 antibody-treated mouse model of SFTS, we observed substantial bone marrow myelopoiesis, marked by an increase in granulocyte-macrophage progenitors (GMP), and a decrease in common lymphoid progenitors (CLP) and megakaryocyte-erythroid progenitors (MEP), which correlated with disease severity. Additionally, we found that SFTSV-infected IgG+ B cells preferentially migrate to the bone marrow, where they accelerate myelopoiesis by expressing pro-inflammatory cytokines. Our findings suggest that the hematological abnormalities in SFTS are driven by dysregulated hematopoiesis, presenting a potential therapeutic target.
Abstract
Discovery of novel antiviral compounds targeting 3CL protease of SARS-CoV-2
Myung Kyu Lee1, Mianling Yang2, Byungil Kim 1, Peng Zhan*,2, and Meehyein Kim*,1
1Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology (KRICT), Daejeon, 34114, Republic of Korea
2Department of Medicinal Chemistry, Key Laboratory of Chemical Biology, Ministry of Education, School of Pharmaceutical Sciences, Shandong University , Ji’nan, 250012, China
The main protease (Mpro, also known as 3CLpro) is categorized as a cysteine protease in the form of a homodimer, with the specific function of recognizing and cleaving polyproteins (pp1a and pp1ab) into Nsp4-Nsp16. Due to its pivotal role for the production of mature viral proteins within the viral life cycle and the absence of human proteases exhibiting comparable cleavage specificity, Mpro has emerged as an ideal target for drug design aimed at treating SARS-CoV-2 infection. In previous studies, we have reported that derivatives of carmofur effectively suppress the protease activity with IC50 values between 0.35 and 0.37 mM and reduce SARS-CoV-2 infection in Calu-3 cells with EC50 values between 20 and 30 mM (1). In a separate study, we utilized a click chemistry-based miniaturized synthesis approach for the direct screening for the SARS-CoV-2 Mpro. For rapid discovery of potent inhibitors targeting SARS-CoV-2 main protease (Mpro), focused libraries comprising 268 compounds were established on 96-well plates utilizing click chemistry. Through in-situ screening, derivatives of a novel scaffold were identified as potent Mpro inhibitors with significant anti-SARS-CoV-2 activity. Notably, C5N demonstrated sub-micromolar Mpro inhibitory potency and excellent antiviral activity in Calu-3 cells at non-toxic concentrations (2). C5N showed superior potency to nirmatrelvir and similar efficacy to ensitrelvir. Importantly, this compound displayed considerable antiviral activities against various SARS-CoV-2 variants as well as HCoV-OC43 and HCoV-229E, indicating its potential broad-spectrum pan-coronaviral activity. Utilizing reverse genetics technology, it was proved that C5N exhibits persistent antiviral activity against nirmatrelvir-resistant SARS-CoV-2 strains with mutations T21I/E166V and L50F/E166V in Mpro. This study presents a paradigm for the rapid identification of enzymatic inhibitors and provides a potential candidate for the development of drugs targeting SARS-CoV-2.
- K. M. Kang, Y. Jang, S. S. Lee, M. S. Jin, C.-D. Jun**, M. Kim***, Y.-C.*, 2023, European Journal of Medicinal Chemistry, 260:115720
- M. Yanga,+, M. K. Leeb,+, S. Gaoa,+, L. Songa,+, H.-Y. Jangb, I. S. Job, C. Kob, S. Wanga, B. Yea, X. Shia, J. Lia, M. Gua, C. E. Müllerc*, X. Liua*, M. Kimb*, P. Zhana*, 2024, Under Review
Abstract
The heterogeneity of steady-state CD4 T cells in mice and their impact on cytokine-dependent bystander response in autoimmune disease and cancer
Min-Ji Cho, Jae-Won Yoon, Sookyung Cho Je-Min Choi
Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 04763, Republic of Korea
Antigen-specific immune responses generated by T cells are a hallmark of adaptive immunity. However, various types of T cells have been identified that exhibit nonconventional roles, such as TcR-independent bystander activation with effector functions during inflammation. Recent advances in single-cell transcriptomic analysis have unveiled unique subpopulations within cells that are generally recognized as homogeneous populations. Here, we investigated unique subpopulations in CD62LhighCD44low naïve CD4 T cells and CD62lowCD44high memory-phenotype (MP) CD4 T cells in steady-state mice, which might have nonconventional roles during inflammation. We identified clearly distinct effector-like MP CD4 T cells which are required to develop or exacerbate autoimmune encephalomyelitis via the Bhlhe40/GM-CSF axis in a bystander manner. Additionally, we identified a unique subpopulation of naïve CD4 T cells that respond to IL-12 and IL-18 to produce IFN-g even without TcR stimulation. These cells can efficiently suppress tumor growth and induce tumor cell death. There are relevant human naïve CD4 T cell subpopulations correlated with anti-PD-1 therapy responsiveness and severity of COVID-19. These results highlight the importance of nonconventional role of unique subpopulations from both naïve and memory-phenotype CD4 T cells, which could be an important target for controlling autoimmune disease, cancer, and infection.
Abstract
Mechanisms of Adjuvant-Elicited Cellular Immunity not revealed by infectious biology.
Contributing authors: Ross M. Kedl, Jared Klarquist, Daria Ivanova, Scott Thompson, Michael Harbell, Tonya Brunetti, and Laurent Gapin
University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
The last 20 years of work have revealed that the vaccine adjuvant elicited T cell response is counterintuitively motivated by immunological signals and pathways that are fundamentally different than those that motivate T cell responses against an active infection. More specifically, our data support the novel hypothesis that Tvacs sustain exponential clonal expansion, energy production, and redox management through an unusual integration of transcriptional and metabolic pathways that do not normally coexist in T cells responding to infectious challenge.
Using various vaccine adjuvant administration in B6 mice, we measure numerous features of the innate and adaptive immune response including inflammatory cytokine correlates of adaptive outcomes, T cell expansion and cell fate decisions, metabolic pathway dependence/utilization, and memory cell development, longevity and protective capacity. We have identified numerous factors which quantitatively regulate the adjuvant-elicited cellular immune responses but not cellular responses to infectious challenge. This list of factors includes cytokines (IL-27, IL-15) 1, transcription factors (Tbet, FOXO1) 2, metabolic pathways (OxPhos vs glycolysis) 1, and even the presence or absence of B cells 3.
We believe that these mechanistic insights are critical to the future application of vaccines for therapeutic purposes and cannot be gained by evaluation of cellular immunity generated in response to infectious challenge. We eventually hope to exploit these mechanisms in developing clinically relevant methods of therapeutic vaccination against diseases such as chronic infections and cancer.
1 Klarquist, J. et al. Clonal expansion of vaccine-elicited T cells is independent of aerobic glycolysis. Sci Immunol 3 (2018). https://doi.org:10.1126/sciimmunol.aas9822
2 Ivanova, D. L. et al. Vaccine adjuvant-elicited CD8(+) T cell immunity is co-dependent on T-bet and FOXO1. Cell Rep 42, 112911 (2023). https://doi.org:10.1016/j.celrep.2023.112911
3 Klarquist, J. et al. B cells promote CD8 T cell primary and memory responses to subunit vaccines. Cell Rep 36, 109591 (2021). https://doi.org:10.1016/j.celrep.2021.109591
Abstract
CD8 Treg-mediated immune regulation in inflammation
Hye-Jung Kim
Department of Immunology, Genentech, San Francisco, USA
Regulatory T cells (Treg) are pivotal mediators of immune regulation, playing a crucial role in maintaining immune homeostasis both under steady-state conditions and during pathophysiological challenges. The disruption of CD8 Treg-mediated recognition of Qa-1-restricted self-antigens can lead to dysregulated immune responses, tissue damage, autoimmune diseases, and inflammation. The identification of the Helios transcription factor and the surface marker Ly49 as critical elements for the differentiation and function of CD8 Treg has significantly advanced our understanding of the unique genetic program of these cells. In this presentation, recent advancements in our comprehension of CD8 Treg will be introduced, with a focus on their lineage commitment, differentiation, and stability. Developmentally, a CD8 lineage is instructed to differentiate into CD8 Treg by a restricted set of TCRs that recognize MHC-E (Qa-1 in mice, HLA-E in humans) and several dominant self-peptides. The recognition and elimination of pathogenic target cells expressing these Qa-1-self-peptide complexes selectively inhibit pathogenic antibody responses without generalized immune suppression. Understanding the TCR-dependent differentiation and target recognition by this lineage of CD8 Treg could pave the way for novel therapeutic approaches aimed at inhibiting pathogenic antibody responses in autoimmune diseases and inflammatory conditions.
Abstract
Immune cell communication in healthy and inflamed human tissues
Martin Prlic
Fred Hutchinson Cancer Center, Seattle, WA, USA
Health and inflammation tend to be considered mutually exclusive states for tissues, however a baseline of inflammation is present even in healthy human tissues, particularly barrier tissues. Human barrier tissues are exposed to a range of environmental stimuli, including but not limited to differences in commensal colonization, frequency of exposure to pathogens and tissue injuries. Failure to resolve inflammatory processes leads to chronic inflammation and disease. Defining which activating and inhibitory signals are present in human tissues and how they affect T cell responsiveness and function is challenging: the etiological stimuli for immune activation in human tissues are typically poorly defined, access to healthy and inflamed/infected tissues from properly matched cohorts, and to tissues that are large enough in size for a comprehensive multi-omic analysis are often limited. Previous studies have demonstrated that inhibitory mechanisms and negative feedback loops are in place soon after a T cell is successfully activated to temporally limit and restrain effector function, which is critical to prevent excessive tissue destruction. Some of these inhibitory signals are CD8 T cell intrinsic and others are provided by professional antigen-presenting cells (APCs), regulatory T cells (Tregs), cytokines and metabolites. We set out to define the signals that regulate the balance of cytotoxicity vs. tissue protection mediated by T cells in inflamed human tissues. Identifying these immunological mechanisms is relevant as it will help provide insight to ultimately allow for selective therapeutic targeting of immune cell subsets to treat chronically inflamed oral tissues.
Abstract
Regulation of IL-15-induced bystander CD8+ T cell activation in viral infection
Eui-Cheol Shin, MD, PhD
The Center for Viral Immunology, Korea Virus Research Institute, IBS, Daejeon, Korea and
Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea
During viral infection, pre-existing memory CD8+ T cells that are not specific for the infecting virus can be activated by cytokines without cognate antigens, termed bystander activation (Kim et al. Immunity 2018, 48:161-173). Bystander-activated CD8+ T cells exert either protective or detrimental effects on the host depending on the infection model or disease (Lee et al. Nat Immunol 2022, 23:13-22). Recently, my laboratory investigated regulatory mechanisms of TCR-independent bystander CD8+ T cell activation. We found that TCR signals suppress characteristic features of IL-15-induced CD8+ T cell activation, including the increased NKG2D expression and upregulation of genes related to NK cell-mediated cytotoxicity and IFN response. Furthermore, we found that Ca2+/calcineurin signaling pathway is responsible for TCR-mediated suppression of IL-15-induced bystander activation. Interestingly, calcineurin inhibitors could not suppress IL-15-induced bystander activation and paradoxically increased IL-15-induced NKG2D expression in the presence of TCR signals. Additionally, we defined genes upregulated by IL-15 and downregulated by concurrent TCR signals as a “bystander activation-specific gene set” and found the upregulation of this gene signature in bystander CD8+ T cells from patients with hepatitis A virus infection, a prototype disease with immunopathology mediated by bystander-activated CD8+ T cells. Our study paves the way for further investigation of bystander CD8+ T cell activation in various pathological conditions and its regulation.
Abstract
Early activation and fate commitment in T cells
Veronika Niederlova, Ales Drobek, Veronika Cimermanova, Juraj Michalik, Ondrej Stepanek
Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences
Upon encountering their cognate antigen, CD8 T cells proliferate and differentiate into potent effector and long-lived memory T cells. There is no consensus when and how this key T-cell memory vs. effector fate decision is made. However, modulating the outcome of this decision might be an important approach in immunotherapies.
This project started by generating an atlas of steady-state CD8 T cells in mice. We identified a novel subset of cells, which expressed a unique set of genes, including those involved in the polyamine metabolism. We called them Tpam cells. Subsequent experiments revealed that this cell stage had signs of very recent antigenic experience and was transient and reversible in nature.
Using monoclonal T cells and infection models in vivo, we found out that Tpam cells are very early activated CD8 T cells even before the first cell division. In the next step, we generated an atlas of T cells responding to the course of infection using our and previously published scRNAseq data. This analysis suggested that Tpams represent only one of two possible fates of activated T cells. Subsequently, we analyzed the phenotype of early activated T cells by scRNAseq and tracked their fates after the adoptive transfer to synchronized infected hosts. Overall, our data suggested an early dichotomy between memory (memory precursor pathway) and effector T cells (Tpam pathway) even before the first division of an activated CD8 T cell.
Abstract
Preparing better vaccines against influenza viruses
Jong Hyeon Seok, Jineui Kim, Jeonghun Kim, Jaehwan You, Joon-Yong Bae, Jin Il Kim, Kisoon Kim, and Man-Seong Park
Department of Microbiology, the Institute of Viral Diseases, Korea University College of Medicine, Seoul, 02841, Republic of Korea
The H3N2 influenza A virus remains a significant global health concern, and demands better vaccines to cover its diverse strains, amid the ongoing risk of vaccine mismatch. Hemagglutinin (HA), a major viral surface glycoprotein, facilitates viral attachment and entry, making it an attractive vaccine antigen. However, immune responses often target epitopes prone to mutation rather than conserved epitopes. Here, we propose a strategy to enhance the cross-reactivity of H3N2 HA by modifying N-linked glycosylation (NLG) sites. Through strategic NLG modifications at specific sites on the HA protein of the virus vaccine candidate, we aim to achieve immune redirection towards the production of broadly neutralizing antibodies capable of binding and neutralizing a broader range of H3N2 strains, with a particular focus on targeting conserved HA stem epitopes. This approach has been confirmed through in vivo efficacy in mice following immunization with the inactivated virus vaccine, demonstrating elicited more cross-reactive antibodies. Our results suggest that NLG modification, as a strategy for developing cross-reactive vaccines, shows promise in reducing the impact of seasonal influenza outbreaks due to vaccine mismatches, extending the interval between vaccine replacements, and represents a promising avenue toward the development of better influenza vaccines.
Abstract
Antibodies against influenza virus neuraminidase
Pavithra Daulagala, Malik Peiris, Hui-Ling Yen
School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
Antibody raised to influenza neuraminidase (NA) protein has been identified as a correlate of protection that reduced viral shedding and alleviated disease severity. We compared the anti-HA and anti-NA antibody profiles of 130 subjects born between 1950-2015 against antigenically distinct A(H1N1) and A(H1N1)pdm09 viruses. By characterizing the N1 antigenic changes of the A(H1N1) viruses, we showed that antigenic changes occurred discordantly between HA and NA, with the N1 drifted less frequently than the H1 proteins. We observed age-dependent imprinting of both anti-HA and anti-NA antibodies against strains circulated during the first decade of life. 67.7% (88/130) and 90% (117/130) of participants developed cross-reactive antibodies to multiple HA and NA antigens at titers ³1:40. As anti-NA antibodies provides broader cross-reactivity than anti-HA antibodies, we further investigated if the general population possess cross-reactive antibodies against a clade 2.3.4.4b A(H5N1) virus that is currently posing a pandemic threat. Using sera collected in 2020 from 63 healthy adults, we detected no hemagglutination inhibition (HAI) antibodies but high titers (geometric mean titer at 1:41.34) of cross-reactive NA inhibition (NAI) antibodies against a clade 2.3.4.4b A(H5N1) virus in 61 of 63 subjects. The use of mono-specific archival ferret anti-sera raised against seasonal A(H1N1) and A(H1N1)pdm09 influenza showed that cross-reactive NAI response to A(H5N1) were elicited by A(H1N1)pdm09, but not seasonal A(H1N1) viruses circulating from 1977-2007. Further analysis on sera of 50 healthy blood donors collected prior to the 2009 pandemic detected low cross-reactive NAI antibodies (geometric mean titer at 1:8.35) to A(H5N1) in 21 of 50 subjects. Our results suggest that the cross-reactive NAI antibodies against A(H5N1) may derived from exposing to the conserved epitopes shared between the avian-origin A(H1N1)pdm09 and avian N1 proteins. Taken together, our results support the inclusion of NA antigens in seasonal and pandemic influenza vaccine preparations.
Abstract
Capless Self-amplifying mRNA Vaccine Induces Robust Immune Response Against Highly Pathogenic Avian Influenza 2.3.4.4 H5 Virus
Min-Suk Song
Department of Microbiology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Chungbuk, Republic of Korea
This study presents a novel self-amplifying mRNA (samRNA) platform that incorporates a unique virus replicon distinct from traditional alphavirus-based systems. Enhanced with its own internal ribosome entry site (IRES), this innovative approach eliminates the need for capping, thus simplifying vaccine production. In comparative analyses, our capless smaRNA (CLsamRNA) exhibited significantly higher luciferase expression levels than conventional mRNA, both in vitro and in vivo. We encapsulated both saRNA and mRNA, each containing the hemaglutinin (HA) gene from the highly pathogenic avian influenza (HPAI) 2.3.4.4 H5 strain, within lipid nanoparticles. Notably, neutralizing antibody titers induced by just 0.1 μg of the saRNA were comparable to those produced by 10 μg of traditional mRNA vaccines. Additionally, the saRNA triggered two to three-fold higher CD8 T cell responses compared to its mRNA counterpart. Importantly, all mice immunized with the saRNA vaccine showed full survival and prevented systemic spread after exposure to the HPAI H5N8 virus, in contrast to the partial protection observed with higher dosages of mRNA vaccines. These findings demonstrate that our novel CLsamRNA platform can induce potent immune responses at significantly reduced dosages, offering a potential reduction in production costs. The technology holds significant promise for rapid vaccine development to combat infectious diseases and as a versatile new therapeutic vector, potentially making a substantial impact on global health.
Registration
Registration Period
June 19th – July 9th
Registration Fee
Student: 50,000 KRW
Regular: 100,000 KRW
Organizers
Host
Sponsor
Venue
2F, Grand Ballroom, Daejeon Convention Center 1 (DCC 1), Daejeon, South Korea
107 Expo-ro, Yuseong-gu, Daejeon, South Korea, 34125