Speakers
Keynote Speakers
Speakers
Abstracts for Oral Presentation
Name & Affiliation:
George F. Gao
Founder of World Flu Day
CAS Key Laboratory of Pathogenic Microbiology and Immunology, The Institute of Microbiology of the Chinese Academy of Sciences
Founder of World Flu Day
CAS Key Laboratory of Pathogenic Microbiology and Immunology, The Institute of Microbiology of the Chinese Academy of Sciences
Title: Comparative Studies on the pandemic viruses: Preparation based on the One Health concept
Abstract:
In the past hundred years, human population expansion and globalization have changed the pattern of human-nature interactions and accelerated the emergence and spread of novel infectious diseases. Among the microbial threats, pandemic-causing viruses have profound and far-reaching impacts on public health, the economy, and society. As two pandemic-risk viruses, it raises concerns on comparative studies on SARS-CoV-2 and influenza viruses themselves, and their interactions with the human population, the animal and the environment in the One Health concept. SARS-CoV-2 and influenza viruses have many common characteristics which may correlate with the driving force of pandemics. The respiratory tract as the transmission route enables the disease to spread globally in a short time. The considerable number of latent or asymptomatic infections and mild cases brings difficulty to the control of the diseases. Emerging viral variants present alarming characteristics, including increased transmissibility and infectivity, alternative drug resistance, and immune escape. The wide range of animal hosts for the influenza viruses and the diverse susceptible animals of SARS-CoV-2 and the related coronaviruses provides potentials for re-emergence, though the animal reservoir has not been confirmed. Thus, the common features of the two viruses imply that knowledge can be shared in the control of the potential pandemic in the future.
Biography:
Gao is a member (academician) of Chinese Academy of Sciences (CAS), an international member of the U.S. National Academy of Sciences (NAS), a foreign member of the U.K. Royal Society (RS), a member of the German National Academy of Sciences Leopoldina. He is a professor of Institute of Microbiology, CAS, a member of WHO Science and Technology Expert Group, a member of WHO One Health High-Level Expert Panel. Gao has pioneered and made numerous significant original breakthroughs on the pathogenesis mechanisms and pathogen-host interaction of emerging infectious pathogens. His interests also include global public health and health strategy, and is an advocate of international collaboration in global public health. Gao pioneers the COVID-19 research and control with virus discovery, vaccine and therapeutic monoclonal antibody development etc.
Name & Affiliation:
Kwok-Yung Yuen
Founder of World Flu Day
Department of Microbiology, The University of Hong Kong
Founder of World Flu Day
Department of Microbiology, The University of Hong Kong
Title: Preparation for the next pandemic: lessons since 1997
Abstract:
Animal surveillance in Hong Kong SAR between 1997 to 2019 has identified many animal influenza viruses and over 30 novel coronaviruses (CoV). Some of these viruses or their close relatives have subsequently jump into humans several years later. This is best exemplified by the bat SARS related CoV found in 2005 which turns out to be the ancestral virus of 2003 SARS-CoV-1 and 2019 SARS-CoV-2. The bat CoV -HKU4 and -HKU5 are closely related to the human and camel MERS-CoV of the 2012 outbreak in Middle East. The relative of porcine DeltaCoV-HKU15 found in 2012 was reported to infect Haitian children in 2021. However, often only the full genome sequences of these 30 novel animal CoVs are available because the majority of them cannot be cultured in vitro. Since most of these animal CoVs are found in enteric specimens while human CoVs are more often found in respiratory specimens, we use adult stem cells harvested from bat intestinal tissue and human lung tissue for setting up three dimensional (3D) organoids for the isolation and characterization of some CoVs known to have health or public health significance. Multiplexed rapid diagnostic assay, broad spectrum antiviral, versatile vaccine platform, and reusable personal protective equipment are also important in preparedness against future pandemics.
Biography:
Professor Kwok-Yung Yuen and his laboratory discovered and characterised many important novel emerging viruses that affect humans and animals. He was the first to report on the unusual severity of influenza A(H5N1)/1997. He found that the structural protein of the viral nucleoprotein can be an antiviral target.
During the 2003 severe acute respiratory syndrome (SARS) outbreak, Professor Yuen and his team discovered the human SARS coronavirus. During the pursuit for the natural animal reservoir for SARS coronavirus, Professor Yuen was the first to discover the bat SARS related coronavirus in Chinese horseshoe bats in 2005. Realising that emerging infections will be increasingly important with the rising global population, and therefore the encroachment of human habitat with that of wild animals could lead to intrusion of animal viruses into the human population, Professor Yuen conducted an intensive search that resulted in the discovery and characterisation of more than 80 new viruses or novel genotypes from domestic and wild animals. Of the 30 coronaviruses in this list, the bat coronavirus HKU4 and HKU5 found in 2007 are close relatives of the 2012 Middle East respiratory syndrome coronavirus (MERS-CoV). The porcine coronavirus HKU15 found in 2012 is related to the 2022 porcine deltacoronavirus which jumped into human. The bat SARS-related coronavirus found in 2005 is closely related to the 2019 pandemic SARS-CoV-2. The human coronavirus HKU1 which causes seasonal common cold and chest infections. Professor Yuen is the first to report on the person-to-person transmission of SARS-CoV-2 in a Shenzhen family cluster in 2020.
In addition, Professor Yuen also found that the rattus Hepatitis E virus species C can jump into human and cause clinical disease. He has also discovered over 20 novel bacterial, fungal and parasitic species. Besides setting up diagnostic tests for hunting novel viruses or managing patients, Professor Yuen has identified viral pathogenic mechanisms which can be translated into novel host targets for broad spectrum antivirals.
Professor Yuen’s laboratory is dedicated to the control of emerging infectious diseases.
During the 2003 severe acute respiratory syndrome (SARS) outbreak, Professor Yuen and his team discovered the human SARS coronavirus. During the pursuit for the natural animal reservoir for SARS coronavirus, Professor Yuen was the first to discover the bat SARS related coronavirus in Chinese horseshoe bats in 2005. Realising that emerging infections will be increasingly important with the rising global population, and therefore the encroachment of human habitat with that of wild animals could lead to intrusion of animal viruses into the human population, Professor Yuen conducted an intensive search that resulted in the discovery and characterisation of more than 80 new viruses or novel genotypes from domestic and wild animals. Of the 30 coronaviruses in this list, the bat coronavirus HKU4 and HKU5 found in 2007 are close relatives of the 2012 Middle East respiratory syndrome coronavirus (MERS-CoV). The porcine coronavirus HKU15 found in 2012 is related to the 2022 porcine deltacoronavirus which jumped into human. The bat SARS-related coronavirus found in 2005 is closely related to the 2019 pandemic SARS-CoV-2. The human coronavirus HKU1 which causes seasonal common cold and chest infections. Professor Yuen is the first to report on the person-to-person transmission of SARS-CoV-2 in a Shenzhen family cluster in 2020.
In addition, Professor Yuen also found that the rattus Hepatitis E virus species C can jump into human and cause clinical disease. He has also discovered over 20 novel bacterial, fungal and parasitic species. Besides setting up diagnostic tests for hunting novel viruses or managing patients, Professor Yuen has identified viral pathogenic mechanisms which can be translated into novel host targets for broad spectrum antivirals.
Professor Yuen’s laboratory is dedicated to the control of emerging infectious diseases.
Name & Affiliation:
Sumit Kumar Chanda
Department of Immunology and Microbiology, Scripps Research
Department of Immunology and Microbiology, Scripps Research
Title: Global Analysis of Influenza Host-Pathogen Interaction
Abstract:
A global, multi-OMIC survey including transcriptomic, proteomic and genetic loss-of-function datasets was conducted on human cells infected with IAV strains of different virulence. Integration of these datasets provided insight into the cellular landscape that limits IAV replication in a strain-specific or broadly-acting manner. Additionally, we performed a meta-analysis of RNAi screens to prioritize host and restriction factors that were found to impact viral replication in multiple datasets. These studies captured both constitutive and interferon-inducible antiviral mechanisms. Notably, all three OMICs datasets identified the autophagy TBC1 Domain Family Member 5 (TBC1D5) as a constitutive IAV restriction factor in vitro and in vivo. TBC1D5 interacts with the small GTPase Rab7 to regulate its activation state, which in turn controls vesicle trafficking and cargo degradation by autophagy. During IAV replication, matrix 2 (M2) protein interacts with TBC1D5, thereby displacing Rab7 and resulting in less M2 degradation. Additionally, our multi-OMIC studies revealed that the M2 protein associates with the putative ubiquitin ligase UBR4, to avoid autophagosome targeting and promote apical transport of viral proteins to enable viral egress. WE propose that UBR4 and TBC1D5 are participants in a wider, unfolded protein response (UPR)-based defense mechanism that restricts viral replication. M2 interference with UPR factors is a major strategy of IAV escape from this intrinsic antiviral mechanism.
Biography:
Sumit Chanda earned his Ph.D. from Stanford University in 2001 and received his post-doctoral training at the Genomics Institute of the Novartis Research Foundation (GNF). He subsequently transitioned to a Group Leader position and established his research group in the Division of Cellular Genomics at GNF. In 2007, he joined the Infectious and Inflammatory Disease Center at Sanford-Burnham Medical Research Institute as an Associate Professor. Dr. Chanda was promoted to Professor in 2013. In 2015, he was appointed Director of the Immunity and Pathogenesis Program at Sanford Burnham Prebys Medical Discovery Institute. He joined Scripps in 2021 as Professor of Immunology and Microbiology. In his free time, Sumit enjoys soccer, scuba-diving, hiking and trying new restaurants.
Name & Affiliation:
Adolfo Garcia-Sastre
Icahn School of Medicine at Mount Sinai
Icahn School of Medicine at Mount Sinai
Title: Towards a universal influenza virus vaccines
Abstract:
During infection, viruses are exposed to multiple selection pressures imposed by the host’s innate and adaptive immune system. Like other pathogenic RNA viruses, SARS-CoV-2 has evolved a diverse set of antagonistic strategies that aim at the modulation of cellular innate immune pathways to favor viral replication and spread. We have shown that the accessory protein ORF6 is a powerful antagonist of the interferon (IFN) signaling pathway by interacting with the Nup98-Rae1 complex at the nuclear pore, and disrupting bi-directional nuclear-cytoplasmic trafficking. An ORF6-deficient SARS-CoV-2 recombinant virus is not able to effectively block IFN signaling and host mRNA nuclear export resulting in a significant reduction of virus pathogenicity in vivo.
Biography:
Prof Adolfo García-Sastre is Professor in the Departments of Microbiology and Medicine, and Director of the Global Health and Emerging Pathogens Institute of Icahn School of Medicine at Mount Sinai in New York, NY. He is also Principal Investigator for the Center for Research on Influenza Pathogenesis and Transmission (CRIPT), one of five NIAID Centers 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 600 peer-reviewed publications in these areas of research. In 2017, he was elected as a fellow of the Royal Academy of Pharmacy in Spain, and in 2019, he was elected to the National Academy of Sciences.
Name & Affiliation:
Alexender Shestopalov
Ministry of Science and Higher Education of the Russian Federation, Institute of Virology of the Federal Research Center for Fundamental and Translational Medicine
Ministry of Science and Higher Education of the Russian Federation, Institute of Virology of the Federal Research Center for Fundamental and Translational Medicine
Title: The Avian influenza in wild birds at the Asian part Russia: the continuation of H5Nx viruses’ story
Abstract:
The main aim of the work is to conduct the surveillance of the influenza virus in wild birds’ population of Northern Eurasia (the Asian part of Russia), to assess the genetic diversity and phylogenetic relationships of highly pathogenic avian influenza viruses circulating in the Asian part of Russia in 2020-2022.
At the territory of the Asian part of Russia (especially on the Western Siberian Plain) there are a huge number of rivers and lakes which are situated on the way of migration of many bird species and are breeding ranges of a large number of species that are ecologically related to reservoirs. Thus, in the Asian part of Russia there are favorable conditions for the spreading of variable influenza viruses. During the birds’ surveillance, more than 150 influenza viruses of various subtypes were identified and isolated.
During the researching period sequencing of all eight genome segments of 35 influenza A virus strains were performed, the analysis showed that those viruses belong to H5 subtype. According to the phylogenetic analysis all H5 strains belong to clade 2.3.4.4b and are highly pathogenic.
The monitoring showed the distribution of new reassortant variants of AIV, including HP AIV, from the Western Siberia to the European part of Russia.
The work was supported by the RNF 22-64-00044 project «Investigation of viral metapopulations in migrating birds of the Asian part of Russia and China for early detection of new variants of viral pathogens.
At the territory of the Asian part of Russia (especially on the Western Siberian Plain) there are a huge number of rivers and lakes which are situated on the way of migration of many bird species and are breeding ranges of a large number of species that are ecologically related to reservoirs. Thus, in the Asian part of Russia there are favorable conditions for the spreading of variable influenza viruses. During the birds’ surveillance, more than 150 influenza viruses of various subtypes were identified and isolated.
During the researching period sequencing of all eight genome segments of 35 influenza A virus strains were performed, the analysis showed that those viruses belong to H5 subtype. According to the phylogenetic analysis all H5 strains belong to clade 2.3.4.4b and are highly pathogenic.
The monitoring showed the distribution of new reassortant variants of AIV, including HP AIV, from the Western Siberia to the European part of Russia.
The work was supported by the RNF 22-64-00044 project «Investigation of viral metapopulations in migrating birds of the Asian part of Russia and China for early detection of new variants of viral pathogens.
Biography:
Shestopalov Alexander Mikhailovich is the author of more than 440 scientific publications, including 4 monographs, 44 patents for inventions and utility models.
The area of scientific interests is virology, zoonotic infections, ecology and pathogenesis of infectious diseases caused by viruses in humans and animals, oncological diseases, development of diagnostic and therapeutic drugs. Created by Professor Shestopalov, scientific school “Ecological polymorphism and territorial significance of current zoonotic infections: control, diagnosis, methods of prevention and treatment” is widely known in Russia and abroad. Alexander Shestopalov is one of the authors of the development of criteria for assessing the environmental and social significance of new and re-emerging viral zoonotic infections; development of a statistical GIS model of the impact of climate change on the detection of viral infections in Siberia and the Far East. Under the leadership of Professor Shestopalov, as part of an international project together with the Institute of Microbiology of the Chinese Academy of Sciences (Beijing), a system for assessing the risk of the emergence of new influenza viruses in Central Asia (Russia, China) was developed.
Alexander Shestopalov created lecture courses “Ecology of zoonotic infections” (China-Russian Institute of Heilongjiang University, Harbin, China); “Creation of databases for medical and environmental research”, “Modern environmental problems of the Caspian region” (Institute of Ecology and Sustainable Development of Dagestan State University, Makhachkala, Russia), Alexander Shestopalov and his students, in collaboration with Imbian Lab LLC (Novosibirsk), developed test systems for the rapid diagnosis of the disease caused by SARS-CoV-2 based on ELISA (3 kits) and PCR based (1 kit).
Professor Shestopalov is the Russian coordinator of the Asian branch of the International Ornithological Society (head of the department is Professor Lei Fumin, Institute of Zoology, Chinese Academy of Sciences, Beijing, China), a member of OFFLU (the joint global network of OIE and FAO experts in the field of animal influenza).
For his achivements Alexander Shestopalov was awarded diplomas and letters of gratitude from the governor, the legislative assembly of the Novosibirsk region, the Novosibirsk regional council of deputies, and the Minister of Health of the Russian Federation. For his study of highly pathogenic avian influenza viruses of the H5N1 subtype, he was awarded the “Novartis Vaccine Award for Epidemiology of Infectious Diseases” by the US Society for the Study of Infectious Diseases. In 2023, he was awarded the state title “Honorary Scientist of the Russian Federation”.
The area of scientific interests is virology, zoonotic infections, ecology and pathogenesis of infectious diseases caused by viruses in humans and animals, oncological diseases, development of diagnostic and therapeutic drugs. Created by Professor Shestopalov, scientific school “Ecological polymorphism and territorial significance of current zoonotic infections: control, diagnosis, methods of prevention and treatment” is widely known in Russia and abroad. Alexander Shestopalov is one of the authors of the development of criteria for assessing the environmental and social significance of new and re-emerging viral zoonotic infections; development of a statistical GIS model of the impact of climate change on the detection of viral infections in Siberia and the Far East. Under the leadership of Professor Shestopalov, as part of an international project together with the Institute of Microbiology of the Chinese Academy of Sciences (Beijing), a system for assessing the risk of the emergence of new influenza viruses in Central Asia (Russia, China) was developed.
Alexander Shestopalov created lecture courses “Ecology of zoonotic infections” (China-Russian Institute of Heilongjiang University, Harbin, China); “Creation of databases for medical and environmental research”, “Modern environmental problems of the Caspian region” (Institute of Ecology and Sustainable Development of Dagestan State University, Makhachkala, Russia), Alexander Shestopalov and his students, in collaboration with Imbian Lab LLC (Novosibirsk), developed test systems for the rapid diagnosis of the disease caused by SARS-CoV-2 based on ELISA (3 kits) and PCR based (1 kit).
Professor Shestopalov is the Russian coordinator of the Asian branch of the International Ornithological Society (head of the department is Professor Lei Fumin, Institute of Zoology, Chinese Academy of Sciences, Beijing, China), a member of OFFLU (the joint global network of OIE and FAO experts in the field of animal influenza).
For his achivements Alexander Shestopalov was awarded diplomas and letters of gratitude from the governor, the legislative assembly of the Novosibirsk region, the Novosibirsk regional council of deputies, and the Minister of Health of the Russian Federation. For his study of highly pathogenic avian influenza viruses of the H5N1 subtype, he was awarded the “Novartis Vaccine Award for Epidemiology of Infectious Diseases” by the US Society for the Study of Infectious Diseases. In 2023, he was awarded the state title “Honorary Scientist of the Russian Federation”.
Name & Affiliation:
Anne Wyllie
Department of Epidemiology of Microbial Diseases, Yale University
Department of Epidemiology of Microbial Diseases, Yale University
Title: Saliva as a reliable sample type for sustainable surveillance and outbreak response efforts
Abstract:
The COVID-19 pandemic presented an unprecedented demand for diagnostic testing. Testing was essential for isolating infected individuals and epidemiological surveillance for public health countermeasures, but was frequently strained by high costs, inadequate infrastructure and supply chain disruptions. To overcome these challenges, we developed a low-cost, open-source test in an effort to deliver equitable testing. Key to this was saliva.
We developed ‘SalivaDirect’ to simplify testing through: demonstrating the sensitivity of saliva for SARS-CoV-2 detection; developing clear self-collection instructions; eliminating collection tubes with preservatives; bypassing nucleic acid extraction; validating each step with reagents and instruments from multiple suppliers; demonstrating stable detection after prolonged periods at elevated temperatures; and establishing a novel regulatory model in the US.
Since being granted emergency use authorization (August 2020), 200+ laboratories across 42 US states have been designated to deploy the SalivaDirect SARS-CoV-2 protocol; more than 10 million tests have been run. SalivaDirect’s open-source, streamlined design allows laboratories to utilize existing infrastructure, thereby facilitating rapid scale up, while enabling quicker turnaround times and ensuring actionable results. Additional approaches, including unsupervised self-collection, direct-to-consumer collection kits, and pooled sample testing, increase autonomy, making it an invaluable option for numerous communities. Recently, we have validated this approach for the detection of influenza A/B, RSV and mpox.
The advances in test innovation throughout the pandemic have demonstrated what could be possible for respiratory pathogens across the board. Our extensive validation of saliva and the international implementation of SalivaDirect has demonstrated saliva as sensitive and reliable for SARS-CoV-2 detection. Importantly, this simplified approach is demonstrating applicability to other infectious diseases. Being less invasive and less resource-intensive than other sample types, saliva-based testing can lead to more equitable and sustainable testing and surveillance programs. As a result, saliva can bolster the public health response, particularly in low-resource and remote environments.
We developed ‘SalivaDirect’ to simplify testing through: demonstrating the sensitivity of saliva for SARS-CoV-2 detection; developing clear self-collection instructions; eliminating collection tubes with preservatives; bypassing nucleic acid extraction; validating each step with reagents and instruments from multiple suppliers; demonstrating stable detection after prolonged periods at elevated temperatures; and establishing a novel regulatory model in the US.
Since being granted emergency use authorization (August 2020), 200+ laboratories across 42 US states have been designated to deploy the SalivaDirect SARS-CoV-2 protocol; more than 10 million tests have been run. SalivaDirect’s open-source, streamlined design allows laboratories to utilize existing infrastructure, thereby facilitating rapid scale up, while enabling quicker turnaround times and ensuring actionable results. Additional approaches, including unsupervised self-collection, direct-to-consumer collection kits, and pooled sample testing, increase autonomy, making it an invaluable option for numerous communities. Recently, we have validated this approach for the detection of influenza A/B, RSV and mpox.
The advances in test innovation throughout the pandemic have demonstrated what could be possible for respiratory pathogens across the board. Our extensive validation of saliva and the international implementation of SalivaDirect has demonstrated saliva as sensitive and reliable for SARS-CoV-2 detection. Importantly, this simplified approach is demonstrating applicability to other infectious diseases. Being less invasive and less resource-intensive than other sample types, saliva-based testing can lead to more equitable and sustainable testing and surveillance programs. As a result, saliva can bolster the public health response, particularly in low-resource and remote environments.
Biography:
Anne Wyllie is a Principal Investigator at the Yale School of Public Health. As compared to the gold standard nasopharyngeal swab, Wyllie’s work has identified saliva as a reliable sample type for the sensitive detection of Streptococcus pneumoniae (pneumococcus) in healthy individuals and more recently, during the COVID-19 pandemic response, for the detection of SARS-CoV-2. Improved detection of the pneumococcus has unveiled hidden reservoirs in older adults which holds importance when new vaccination strategies for preventing pneumococcal disease are being considered. For COVID-19, sampling saliva overcame many of the bottlenecks encountered in the mass testing strategies required to control outbreaks. In an effort to bring access to testing, Wyllie validated and optimized saliva for SARS-CoV-2 detection and developed SalivaDirect: a simple, scalable and importantly, cost-effective method to help alleviate SARS-CoV-2 testing demands. Wyllie’s research group remains devoted to advancing saliva diagnostics, providing public health guidance, and improving community health. She is currently working to expand the SalivaDirect assay for the detection of additional respiratory pathogens including influenza, RSV, and mpox virus. These low-cost, flexible PCR tests can be rapidly implemented for outbreak control or for sustainable community surveillance programs.
Name & Affiliation:
Seiya Yamayoshi
The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute
The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute
Title: Human monoclonal antibodies against Influenza viruses and antiviral medications approved for COVID-19 treatment
Abstract:
Many broadly reactive human monoclonal antibodies against the HA stem of influenza A and B viruses have been obtained as part of strategies to develop an antibody-guided universal influenza vaccine. Similarly, cross-reactive human monoclonal antibodies against the NA head of influenza A and B viruses have attracted attention. We tried to obtain one such monoclonal antibody and characterize it. Our cross-reactive clone recognized NA proteins derived from both influenza A and B viruses and inhibited the sialidase activity of the NA protein. It also protected mice from lethal challenge infection, thereby demonstrating its therapeutic potential.
Three classes of antiviral medications against SARS-CoV-2 have been approved. Nirmatrelvir, an oral agent that targets a SARS-CoV-2 main protease (3CLpro, nsp5), is clinically useful against SARS-CoV-2 including its omicron variants. Since most omicron subvariants have reduced sensitivity to many monoclonal antibody therapies, SARS-CoV-2 resistance to nirmatrelvir is a potential public health concern. We characterized mutant viruses possessing the L50F/E166V or L50F/E166A/L167F substitutions in 3CLpro because these combinations are unlikely to affect virus fitness. However, the growth of both mutant viruses in vitro was slightly delayed. Both mutant viruses showed attenuated phenotypes in the hamster infection model, maintained airborne transmissibility, and were outcompeted by wild-type virus in co-infection experiments in the absence of nirmatrelvir, but less so in the presence of the drug. Our findings suggest that viruses possessing Nsp5-L50F/E166V or Nsp5-L50F/E166A/L167F do not become dominant in nature.
Three classes of antiviral medications against SARS-CoV-2 have been approved. Nirmatrelvir, an oral agent that targets a SARS-CoV-2 main protease (3CLpro, nsp5), is clinically useful against SARS-CoV-2 including its omicron variants. Since most omicron subvariants have reduced sensitivity to many monoclonal antibody therapies, SARS-CoV-2 resistance to nirmatrelvir is a potential public health concern. We characterized mutant viruses possessing the L50F/E166V or L50F/E166A/L167F substitutions in 3CLpro because these combinations are unlikely to affect virus fitness. However, the growth of both mutant viruses in vitro was slightly delayed. Both mutant viruses showed attenuated phenotypes in the hamster infection model, maintained airborne transmissibility, and were outcompeted by wild-type virus in co-infection experiments in the absence of nirmatrelvir, but less so in the presence of the drug. Our findings suggest that viruses possessing Nsp5-L50F/E166V or Nsp5-L50F/E166A/L167F do not become dominant in nature.
Biography:
My research focuses on host-virus interactions during virus replication in the cell, the individual, and the community. I have studied several RNA viruses including ebolavirus, enterovirus A71, influenza virus, and SARS-CoV-2 but I now concentrate on influenza virus and SARS-CoV-2.
Recently, I studied human monoclonal antibodies against influenza virus and SARS-CoV-2 mutant viruses that are resistant to antiviral medications.
Recently, I studied human monoclonal antibodies against influenza virus and SARS-CoV-2 mutant viruses that are resistant to antiviral medications.
Name & Affiliation:
Yuhai Bi
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Title: The public risk of H9N2 avian influenza virus
Abstract:
H9N2 viruses have been reported to be involved in the origin of multiple human-infecting avian influenza viruses, such as H7N9, H10N8, and the recently emerging H3N8. H9N2 viruses have contributed a complete set, or partial internal genes, to the novel human-infecting avian influenza viruses. Poultry that carry H9N2 avian influenza viruses host an optimal environment for viruses of different subtypes to exchange their gene segments with H9N2 avian influenza viruses. Avian influenza viruses with H9N2-derived internal genes would also probably have an increased ability to infect humans. Therefore, poultry that carry H9N2 avian influenza viruses are viewed as genetic incubators for the origin of novel avian influenza viruses that infect humans.
H9N2 avian influenza viruses show low pathogenicity in birds, and H9N2-infected poultry are often subclinical, presenting with no or very few symptoms; however, avian hosts can shed and transmit the viruses to other clinically vulnerable individuals. Notably, H9N2 avian influenza viruses have been identified in domesticated poultry across China, with stable endemic lineages in commercial chicken flocks. Since 2016, H9N2 has also gradually become the dominant avian influenza virus subtype in live poultry markets. Importantly, more than 100 human cases of H9N2 avian influenza virus have been reported as of July, 2022, including more than 50 cases after the outbreak of COVID-19. A retrospective seroprevalence study revealed that human infection with H9N2 exceeded 10% in occupationally exposed populations (eg, poultry workers, including wholesale sellers and food delivery workers) in seven regions of China sampled between 2014 and 2016. In addition, the majority of circulating H9N2.
H9N2 avian influenza viruses show low pathogenicity in birds, and H9N2-infected poultry are often subclinical, presenting with no or very few symptoms; however, avian hosts can shed and transmit the viruses to other clinically vulnerable individuals. Notably, H9N2 avian influenza viruses have been identified in domesticated poultry across China, with stable endemic lineages in commercial chicken flocks. Since 2016, H9N2 has also gradually become the dominant avian influenza virus subtype in live poultry markets. Importantly, more than 100 human cases of H9N2 avian influenza virus have been reported as of July, 2022, including more than 50 cases after the outbreak of COVID-19. A retrospective seroprevalence study revealed that human infection with H9N2 exceeded 10% in occupationally exposed populations (eg, poultry workers, including wholesale sellers and food delivery workers) in seven regions of China sampled between 2014 and 2016. In addition, the majority of circulating H9N2.
Biography:
Yuhai Bi, a Professor and Principle Investigator for the research group of “early-warning and pathogenic mechanism of novel virus”, the director of Biosafety Level 3 Laboratory (BSL-3), in the Institute of Microbiology, Chinese Academy of Sciences. He is the member of CAS Youth Innovation Promotion Association, the winner of the award of Outstanding Young Scholars of National Natural Science Foundation (NSFC), and the winner of VCANBIO Award for Innovations and Breakthroughs in Life Sciences and Medicine. Dr. Bi focuses on the genetic evolution, inter-species transmission and pathogenesis of emerging or re-emerging viruses. As first author or corresponding author, he has published over 70 SCI papers, which have been totally cited over more than 2000 times.
Name & Affiliation:
Bin Cao
Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital
Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital
Title: Combination therapy for severe influenza
Abstract:
Despite significant advancements in preventing and managing patients with influenza, seasonal influenza still leads to high morbidity and mortality. Administering antivirals early has been shown to reduce symptoms and complications. However, the management of severe influenza remains a major challenge, as evidenced by the failure of antiviral combination trials in hospitalized patients. Exploring the clinical benefits of corticosteroids and tocilizumab in COVID-19 may provide insights into potential future research directions involving immunomodulatory interventions in severe influenza. Unfortunately, our understanding of the immune responses in severe human influenza, which may differ from COVID-19, is limited. Arbidol, with its antiviral and immune modulation properties, was used in a trial called Severe Influenza Trial of Arbidol (STAR), and the preliminary findings will be reported in this meeting.
Biography:
Bin Cao M.D. is the Vice President of China-Japan Friendship Hospital, the Director of Department of Pulmonary and Critical Care Medicine (PCCM) at China-Japan Friendship Hospital, the Vice Director of National Center for Respiratory Medicine, and the Vice President of the Institute of Respiratory Medicine at Chinese Academy of Medical Sciences. He has been horned Changjiang Scholar Distinguished Professor by the Chinese Ministry of Education, Distinguished Young Scholar by the National Natural Science Foundation of China, and the National Leader in Science, Technology, and Innovation in China. Bin Cao is currently appointed the President-elect of Chinese Thoracic Society (CTS), the Scientific Advisory Committee member of Chinese Academy of Medical Sciences, the Chairman of the first Professional Committee on Respiratory Oncology of the China Anti-Cancer Association, the Antiviral Group (AVG) member of the International Society for Influenza and other Respiratory Virus Diseases (ISIRV), and the associate editor of the Clinical Respiratory Journal. Bin Cao has been devoted to the research on acute respiratory infections, new emerging respiratory infectious diseases, and systemic characterization of viral pneumonia. His group was the first to propose the concept of viral sepsis worldwide, which is important in the management of patients with critical viral infections. As the first or corresponding author (including co-author), he has more than 190 publications in SCI journals (including 4 in the New England Journal of Medicine, 6 in the Lancet, and 2 in other journals of the Lancet Group). His publications have been cited for more than 38,000 times in total, with 5 ranking among the top 1‰ of the highly cited papers for field derived from the ESI and 4 being incorporated into the WHO or NIH guidelines. He has led or participated in the development of 7 guidelines and is the chief editor of 7 monographs.
Name & Affiliation:
Yixin Chen
School of Life Sciences & School of Public Health, Xiamen University
Title: Two strategies towards the development of universal influenza vaccines: Concept, Preliminary data and Perspective
Abstract:
Influenza viruses cause significant disease burden worldwide annually, highlighting the limitation of current influenza vaccine. The development of an effective universal influenza vaccine has been an urgent task. There are many approaches to develop universal influenza vaccines. Here, we will show our two strategies based on our previous research. Strategy 1 is focused on developing vaccines that specifically target the broad neutralizing epitopes of the HA protein. We initiated the study of influenza viruses in 2004. We reported the discovery of the broad neutralizing antibody 8H5 against the H5N1 subtype in 2006, which demonstrated the existence of conserved neutralizing epitopes on the HA protein. Afterwards, based on several remarkable broad neutralizing anti-HA antibodies we identified, our research turned to the development of universal influenza vaccines. Now, we have demonstrated that glycosylation-modified HA vaccine candidate has potential to become a promising universal influenza vaccine in vitro and in vivo. Strategy 2 focuses on inducing T-cell responses by targeting internal viral proteins. During the COVID-19 pandemic, we developed a nasal spray covid-19 vaccine based on an attenuated influenza virus vector. Through intranasal administration, this vaccine induces both specific and non-specific protective immunity in the respiratory tract, providing broad protection against influenza infection in mice. We believe that it is possible to create a universal influenza vaccine by combining the two above strategies.
Biography:
Yixin Chen is a professor of National Institute of Diagnostics and Vaccine Development in infectious disease at the School of Life Sciences & School of Public Health, Xiamen University. Dr. Chen has been in the field of influenza virus research since 2004 and earned his PhD degree from the School of Life Sciences, Xiamen University in 2009. He first proposed the new concept of ” broad-neutralizing epitope in highly variable influenza virus hemagglutinin” in 2005 and has focused on the development of vaccine, therapeutic agents and diagnostics of influenza, especially for the broad-spectrum neutralizing antibodies and universal influenza vaccines. In recent years, he acts as a key participant in the research of intranasal influenza virus vector-based COVID-19 vaccines, dNS1-RBD, which has proven to have a broad-spectrum protective effect against symptomatic Omicron infection in a randomized placebo-controlled phase III clinical trial, leading to its approval for emergency use in China in 2022.
Name & Affiliation:
Shiho Chiba
The Pandemic Preparedness, Infection and Advanced Research Center, The University of Tokyo
Title: Influenza H3 hemagglutinin vaccine with scrambled immuno-dominant epitopes elicits antibodies directed toward immuno-subdominant head epitopes
Abstract:
Vaccination is the most effective countermeasure to reduce the severity of influenza. Current seasonal influenza vaccines mainly elicit humoral immunity targeting hemagglutinin (HA). In particular, the amino acid residues around the receptor-binding site in the HA head domain are predominantly targeted by humoral immunity as ‘immuno-dominant’ epitopes. However, mutations readily accumulate in the head domain due to high plasticity, which results in frequent antigenic drift and vaccine mismatch, particularly with influenza A(H3N2) viruses. A vaccine strategy that targets more conserved immuno-subdominant epitopes would yield a broadly reactive vaccine.
Here, we designed an H3 HA vaccine antigen with various amino acids at immuno-dominant epitopes of the HA head domain, termed scrambled HA (scrHA). In ferrets, scrHA vaccination induced lower serum neutralizing antibody levels against homologous virus compared with wild-type (WT) HA vaccination; however, similar levels of moderately neutralizing antibody titers were induced against antigenically distinct H3N2 viruses. Ferrets vaccinated with scrHA and then challenged with homologous or heterologous virus showed the same level of reduced virus shedding in nasal swabs as WT HA-vaccinated animals but a smaller increase in body temperature, whereas WT HA-vaccinated ferrets exhibited body temperature increases similar to those of mock-vaccinated animals. scrHA elicited binding antibodies against HA immuno-dominant and immuno-subdominant head epitopes at lower and higher levels, respectively, than WT HA vaccination, whereas anti-stalk antibodies were induced at the same level for both groups, suggesting that scrHA redirects from immuno-dominant to immuno-subdominant epitopes in the HA head domain. scrHA vaccination thus induced broader coverage than WT HA vaccination by diluting out the immuno-dominancy of HA head epitopes.
Here, we designed an H3 HA vaccine antigen with various amino acids at immuno-dominant epitopes of the HA head domain, termed scrambled HA (scrHA). In ferrets, scrHA vaccination induced lower serum neutralizing antibody levels against homologous virus compared with wild-type (WT) HA vaccination; however, similar levels of moderately neutralizing antibody titers were induced against antigenically distinct H3N2 viruses. Ferrets vaccinated with scrHA and then challenged with homologous or heterologous virus showed the same level of reduced virus shedding in nasal swabs as WT HA-vaccinated animals but a smaller increase in body temperature, whereas WT HA-vaccinated ferrets exhibited body temperature increases similar to those of mock-vaccinated animals. scrHA elicited binding antibodies against HA immuno-dominant and immuno-subdominant head epitopes at lower and higher levels, respectively, than WT HA vaccination, whereas anti-stalk antibodies were induced at the same level for both groups, suggesting that scrHA redirects from immuno-dominant to immuno-subdominant epitopes in the HA head domain. scrHA vaccination thus induced broader coverage than WT HA vaccination by diluting out the immuno-dominancy of HA head epitopes.
Biography:
Shiho Chiba is an assistant professor at the Pandemic Preparedness, Infection and Advanced Research Center at the University of Tokyo. She obtained her B.S. in Science (biochemistry and biophysics) from the University of Tokyo, an M.S. in Medical Science (immunology) from the University of Tokyo, and a Ph.D. in Medicine (immunology) from the University of Tokyo under the supervision of Dr. Tadatsugu Taniguchi. Following her Ph.D., she completed a postdoctoral fellowship in the laboratory of Dr. Yoshihiro Kawaoka at the University of Wisconsin-Madison, where she studied molecular virology of influenza viruses. Her recent research has focused on immunogenic and pathogenic analyses of respiratory infectious viruses (influenza viruses and SARS-CoV-2), and host immune responses induced by virus infection and vaccinations.
Name & Affiliation:
Tao Deng
CAS Key laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology of the Chinese Academy of Sciences
Title: The dynamic regulation of influenza virus genome transcription and replication
Abstract:
Influenza virus genome transcription and replication, catalyzed by viral RNA-dependent RNA polymerase (RdRp), are delicately controlled across the virus life cycle. A switch from transcription to replication at mid-to-late stage of an infection is a key event for the virus to produce progeny virions efficiently. However, the underlying mechanisms by which transcription and replication are dynamically regulated remain elusive for years. It is known that viral NS1 and NS2 proteins are expressed with different timings from unspliced and spliced mRNAs of the viral NS segment. In this study, we found that the early expressed NS1 protein can stimulate viral mRNA synthesis, while the late-expressed NS2 protein can inhibit mRNA synthesis but promote vRNA synthesis in a manner highly consistent with the dynamic changes in mRNA/vRNA in the virus life cycle. We also identified key functional amino acids of NS1 and NS2 involved in these regulations. According to our finding that the last amino acid I121 of NS2 plays a critical role in promoting viral genome replication, we further performed 20 amino acid screening at residue NS2-I121 for virus rescue. We found that the hydrophobicity of the residue 121 is essential for the virus survival. Interestingly, through serial passage of the rescued mutant viruses, we identified adaptive mutations PA-K19E and PB1-S713N on the viral RdRp which could effectively compensate for the replication-promoting defect caused by NS2-I121 mutation. we further demonstrated that both wild-type NS2 and PA-K19E/PB1-S713N can enhance the RdRp dimerization that is necessary for vRNA synthesis. Together, we propose that the stoichiometric changes in the viral NS1 and NS2 proteins during infection could be responsible for the dynamic regulation of the viral RNA syntheses.
Biography:
Tao Deng is a professor of Institute of Microbiology, Chinese Academy of Sciences. Prof. Deng has been in the field of influenza virus since 2001. She did her PhD and postdoc in Sir Willian Dunn School of Pathology, Oxford University. She has long been studying the viral ribonucleoprotein complex (vRNP) of influenza viruses, especially interested in how vRNP is assembled in cells and how it carried out the viral genome transcription, replication, and selective packaging. A few of her earlier papers have been cited by the famous text book – Field Virology. In recent years, she has published a series of papers in J Virol and Nat Commun which have made significant contributions in advancing our understanding the detailed molecular mechanisms of influenza virus replication.
Name & Affiliation:
Ivan Fan-Ngai Hung
Department of Medicine, The University of Hong Kong
Department of Medicine, The University of Hong Kong
Title: Strategies to improve immunogenicity of influenza vaccine
Abstract:
Seasonal influenza infection results in half a million death globally every year. The elderlies and patients with chronic illness are at high risk of developing complications and secondary bacterial infection after influenza infection. In this talk, I will review strategies aimed to improve the immunogenicity of influenza vaccines including intradermal vaccination, adjuvanted vaccines, high dose vaccines and other novel influenza vaccines.
Biography:
Professor Ivan Fan Ngai HUNG is Chair of Infectious Diseases, Ru Chien and Helen Lieh Endowed Professor in Health Sciences Pedagogy, Professor of Medicine and Assistant Dean (Admissions), Chief of the Division of Infectious Diseases, Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, and Honorary Consultant in Queen Mary Hospital, Hong Kong. He is also Chair Professor and Chief-of-Service of the Department of Infectious Diseases and Clinical Microbiology at the HKU-Shenzhen Hospital.
Professor Hung has published more than 340 international peer reviewed original articles, including research articles in the Lancet, the Lancet Infectious Diseases, Nature and the Clinical Infectious Diseases. His research interest includes influenza, SARS-CoV-2 and other respiratory virus antiviral treatment and vaccinology. He has pioneered the use of the triple combination of interferon beta-1b, lopinavir/ ritonavir and ribavirin in the treatment of hospitalized COVID-19 patients, resulting in significantly faster clinical alleviation and viral load suppression. He and his team also pioneered the application of topical imiquimod before intradermal influenza vaccination, which results in protection against heterologous non-vaccine and antigenically drifted viruses. He was also the first to prove convalescent plasma and H-IVIG reduced mortality in patients with severe influenza infection in prospective clinical trials. He is ranked as HKU Scholars in the world top 1% in 2013, 2018-2022. He is the world-leading expert in the field of antiviral and vaccinology for influenza and COVID-19 infection. He is currently the Editorial Board member of the Vaccine and Diagnostics medical journals. As a clinician scientist, Professor Hung believes in innovation, team-work and clinical application of translational research in tackling threats from emerging infectious diseases.
Professor Hung has published more than 340 international peer reviewed original articles, including research articles in the Lancet, the Lancet Infectious Diseases, Nature and the Clinical Infectious Diseases. His research interest includes influenza, SARS-CoV-2 and other respiratory virus antiviral treatment and vaccinology. He has pioneered the use of the triple combination of interferon beta-1b, lopinavir/ ritonavir and ribavirin in the treatment of hospitalized COVID-19 patients, resulting in significantly faster clinical alleviation and viral load suppression. He and his team also pioneered the application of topical imiquimod before intradermal influenza vaccination, which results in protection against heterologous non-vaccine and antigenically drifted viruses. He was also the first to prove convalescent plasma and H-IVIG reduced mortality in patients with severe influenza infection in prospective clinical trials. He is ranked as HKU Scholars in the world top 1% in 2013, 2018-2022. He is the world-leading expert in the field of antiviral and vaccinology for influenza and COVID-19 infection. He is currently the Editorial Board member of the Vaccine and Diagnostics medical journals. As a clinician scientist, Professor Hung believes in innovation, team-work and clinical application of translational research in tackling threats from emerging infectious diseases.
Name & Affiliation:
Dongyan Jin
School of Biomedical Sciences, The University of Hong Kong
School of Biomedical Sciences, The University of Hong Kong
Title: Ambivalent modulation of innate immunity by influenza A virus PB1-F2 virulence factor
Abstract:
Seasonal influenza and human infection with highly pathogenic avian influenza A virus (IAV) continue to pose significant public health concerns. PB1-F2 is a small IAV protein translated from the second open reading frame of PB1 region. PB1-F2 contains multiple motifs and regions that have been shown to be influential on the pathogenicity of IAV in a subtype- and host-specific fashion, through multiple mechanisms related to apoptosis, innate interferon (IFN) response, inflammasome assembly and secondary bacterial infection. The influence of PB1-F2 on innate immunity appears to be ambivalent depending on the stage of infection and locations of the protein. We have found that PB1-F2 of avian influenza A (H7N9) virus is particularly potent in the suppression of antiviral signaling. It forms protein aggregates on mitochondria, inhibits TRIM31-MAVS interaction, and prevents MAVS ubiquitination and aggregation. PB1-F2 also suppresses NLRP3 inflammasome activation and IL-1β secretion in infected human monocyte-derived macrophages by inhibiting the interaction between NLRP3 and MAVS. PB1-F2 is also secreted to extracellular space through exosomes, where it induces NLRP3 inflammasome maturation of uninfected macrophages. This activity of PB1-F2 exhibits subtype specificity, in keeping the induction of a pro-inflammatory cytokine storm by H7N9 but not WSN virus. PB1-F2 of H7N9 is also sequestered in the nucleolus, leading to weaken suppression of RNA or DNA sensing. Our findings on subtype-selective and location-dependent modulation of innate immunity by PB1-F2 have implications in viral pathogenesis and antiviral development. Supported by HMRF 19180812.
Biography:
Dong-Yan Jin got his PhD with Prof. Yun-De Hou in Beijing in 1991 and then received postdoctoral training with Dr. Kuan-Teh Jeang at NIAID, NIH in 1994-1999. He joined the University of Hong Kong in 1999 and is now Clare and Lawrence Fok Professor in Precision Medicine. He is a molecular virologist with an interest in viral oncogenesis and innate antiviral response. In his study of human T-cell leukemia virus, he discovered in 1998 a key component named MAD1 of the cellular mitotic checkpoint. This work has been considered seminal in the study of cell cycle. In 2011, his group found that the virus sensor RIG-I needs an RNA-binding protein partner called PACT to initiate and sustain antiviral response. They have also identified and characterized novel viral interferon antagonists and inflammasome activators in SARS-CoV, MERS-CoV and SARS-CoV-2. Many of their findings have not only broken new grounds to understand virus-host interaction and viral pathogenesis, but also revealed new strategies and leads for disease prevention and intervention. He was elected to be Fellow of American Academy of Microbiology in 2020 and serves on Editorial Boards of all major specialty journals in the broad fields of virology, infectious diseases and molecular cell biology.
Name & Affiliation:
Raven Kin-Hang Kok
Department of Microbiology, The University of Hong Kong
Department of Microbiology, The University of Hong Kong
Title: An interferon-integrated SARS-CoV-2 vaccine
Abstract:
A nasal vaccination using a live-attenuated virus has been shown to generate robust and comprehensive immune responses. However, employing an attenuated form of the SARS-CoV-2 virus as a nasal vaccine poses challenges due to potential co-infections, which could result in genetic recombination and the generation of revertant viruses. To address this, we present the Interferon-Beta-Integrated SARS-CoV-2 (IBIS) vaccine, wherein the viral orf8 segment is replaced with type-I interferon. The integration of interferon-beta in the IBIS vaccine helps suppress co-infections, thereby minimizing the risk of natural infection before or after administration. Furthermore, by directly encoding interferon-beta within the vaccine genome, we circumvent the “delayed type-I interferon signaling,” a common pathogenic feature of coronavirus infections. Notably, the live-attenuated IBIS vaccine not only induces robust activation of CD8+ T cells but also facilitates the immediate expression of interferon-beta, which enhances the activation of virus-specific mucosal CD4+ T cells. Through this dual mechanism of action, involving interferon-beta-driven innate protection and augmented adaptive immune responses, the IBIS vaccine overcomes concerns associated with using live-attenuated SARS-CoV-2 as a nasal vaccine, offering broad protection against sarbecoviruses.
Biography:
Dr. Kok is currently an Associate Professor in the Department of Microbiology, The University of Hong Kong. He is a molecular virologist and has been interested in the host-virus interaction and innate immunity including “interferon signaling”. In addition to basic molecular virology study, Dr. Kok and his team recently developed novel vaccines such as intradermal influenza vaccine, nasal NanoComplex protein vaccine, and live-attenuated Universal Sarbecovirus vaccine.
Name & Affiliation:
Yutaka Kuroda
Graduate School of Engineering, Biotechnology and Life Sciences, Tokyo University of Agriculture and Technology
Title: Toward the development of subunit vaccines using small engineered E. coli expressed viral protein domains
Abstract:
Large-scale Escherichia coli (E. coli) production of viral proteins can yield a versatile and low-cost antigen for subunit vaccines, provided the protein is folded correctly. However, most small proteins expressed in E. coli generally have a low immunogenicity, unfit as vaccine antigens.
Here, we use the receptor-binding domain (RBD) of the SARS-CoV-2 as a model protein to assess its potential as an anti-SARS-Cov-2 subunit vaccine. To this end, we show that despite standard E. coli expression protocol would produce RBDs with aberrant disulfide bonds, resulting in insoluble and non-native RBDs, one can optimize expression protocols to yield high-purity RBD folded into a native-like structure, as demonstrated by biophysical and spectroscopic methods. Furthermore, our E. coli-produced RBD elicits a high IgG titer in Jcl: ICR mice and produces neutralizing antisera, as demonstrated by a pseudovirus-based neutralization assay.
Here, we use the receptor-binding domain (RBD) of the SARS-CoV-2 as a model protein to assess its potential as an anti-SARS-Cov-2 subunit vaccine. To this end, we show that despite standard E. coli expression protocol would produce RBDs with aberrant disulfide bonds, resulting in insoluble and non-native RBDs, one can optimize expression protocols to yield high-purity RBD folded into a native-like structure, as demonstrated by biophysical and spectroscopic methods. Furthermore, our E. coli-produced RBD elicits a high IgG titer in Jcl: ICR mice and produces neutralizing antisera, as demonstrated by a pseudovirus-based neutralization assay.
Biography:
I graduated from the Department of Physics at ETHZ (Eidgenossishe Technische Hochschule Zurich), where I conducted my undergraduate research in solid-state physics (one-dimensional superconductor). I obtained a Master’s and a Ph.D. degree under the supervision of Professor Akiyoshi Wada, who introduced me to protein biophysics at the Department of Physics at the University of Tokyo.
Before joining the Department of Biotechnology and Life Sciences at TUAT in 2004, I worked as a senior research scientist at RIKEN (Japan), working on protein structure, folding, and their applications to structural genomics. Before that, I was an HFSP (Human Frontier Science Program) fellow and a Whitehead fellow in Professor Peter S. Kim’s research group at the Whitehead Institute, MIT, for three years until September 1998. Before joining MIT, I was a research scientist at the Protein Engineering Research Institute (PERI) in the group of Dr. Haruki Nakamura, the previous head of the Japanese Protein Data Bank (PDB).
Before joining the Department of Biotechnology and Life Sciences at TUAT in 2004, I worked as a senior research scientist at RIKEN (Japan), working on protein structure, folding, and their applications to structural genomics. Before that, I was an HFSP (Human Frontier Science Program) fellow and a Whitehead fellow in Professor Peter S. Kim’s research group at the Whitehead Institute, MIT, for three years until September 1998. Before joining MIT, I was a research scientist at the Protein Engineering Research Institute (PERI) in the group of Dr. Haruki Nakamura, the previous head of the Japanese Protein Data Bank (PDB).
Name & Affiliation:
Jinhua Liu
Department of Preventive Veterinary Medicine, College of Veterinary Medicine, China Agricultural University
Department of Preventive Veterinary Medicine, College of Veterinary Medicine, China Agricultural University
Title: Emergence and cross-species transmission of H3 subtype avian influenza viruses
Abstract:
The novel avian influenza virus (AIVs) causes not only the poultry diseases, but also poses a threat to public health. We found that the H3N8 virus was emerged in chicken population in China in 2021 and evolved into H3N2 and H3N3 viruses in 2023. H3N8 AIVs caused two confirmed human infections in 2022, followed by a fatal case reported in 2023. H3N8 viruses are widespread in chicken flocks; however, the zoonotic features of H3N8 viruses are poorly understood. Here, we demonstrate that H3N8 viruses were able to infect and replicate efficiently in organotypic normal human bronchial epithelial (NHBE) cells and lung epithelial (Calu-3) cells. Human isolates of H3N8 virus were more virulent and caused severe pathology in miceand ferrets, relative to chicken isolates. Importantly, H3N8 virus isolated from a patient with severe pneumonia was transmissible between ferrets through respiratory droplets; it had acquired human-receptor-binding preference and amino acid substitution PB2-E627K necessary for airborne transmission. Human populations, even when vaccinated against human H3N2 virus, appear immunologically naive to emerging mammalian-adapted H3N8 AIVs. Given that H3 subtype influenza viruses had historically been responsible for pandemic of 1968 Hong Kong flu. Therefore, emergence and prevailing of novel H3 subtype viruses in chicken population should be given highly concerned.
Biography:
Professor Jinhua Liu is director of the Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University (Beijing). Concurrently, he is the chairman of the Avian Epidemiology Branch within the Chinese Association of Animal Science and Veterinary Medicine. His research focuses on anima influenza, including avian, swine, and canine influenza, with special emphasis on their epidemiology, pathogenicity, and cross-species transmission mechanisms. Notably, he was the first to detect the H5N1 viruses in migratory birds at Qinghai Lake (Science, 2005), as well as the H3N8 virus in farm chickens that caused human infection (Lancet Microbe, 2022) and illustrated airborne transmission of human-isolated avian H3N8 influenza virus between ferrets (Cell, 2023). his team has successfully developed a turkey herpesvirus vector-based recombinant H9 HA vaccine, a significant stride towards combating the prevalent H9N2 avian influenza in China.
Name & Affiliation:
Jun Liu
Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention
Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention
Title: The comparative cellular immunology of influenza and COVID-19
Abstract:
The emerging and re-emerging viruses e.g. SARS-CoV-2 and influenza viruses pose a great threaten to public health. Considering the special features such as the conserved targets and long-term durability, the host T-cell provides an unneglectable role during the anti-virus immunity. We established a T cell-based test, surveillance and research platform to investigate the mechanism by which the human T cell immunity reacts to the viruses. We have screened a series of T cell epitopes from SARS-CoV, SARS-CoV-2 and influenza viruses, etc. and utilized these epitopes to investigate the features and mechanisms of antigen-specific cellular immune responses in the patients, convalescents, and vaccinated populations. The comparative cellular immunological studies on COVID-19 and influenza patients during their acute infection and after recovery indicated a series of shared immune features, but also revealed distinct response pathways and indicators. The parallel studies on the immune response after vaccination against these two respiratory viruses are also worth learning from each other. The understanding of T cell mediated immune mechanism to the emerging virus infections will benefit the development of the peptide-based vaccines.
Biography:
Prof. Liu graduated from the School of Public Health, Peking University Health Science Center in 2005. He received a Ph.D degree from Institute of Microbiology, Chinese Academy of Sciences and had the postdoctoral training at Yale School of Medicine. The main research focus of his group is the molecular mechanisms of the CD8+ T cell epitopes presented by MHC class I and the T-cell recognition of emerging and re-emerging viruses, i.e. SARS-CoV-2, influenza viruses etc. He has published more than 170 papers in leading journals such as Nature (×2), Immunity, PNAS, Nat Commun, EID, CID, JID, J Virol (×10) and J Immunol (×9), etc. He is the Assistant Secretary of Asia-Pacific Biosafety Association, the deputy Editor-in-Chief of Biosafety and Health, and editor for Infectious Diseases & Immunity, Global Transitions, and invited guest editor of Frontiers in Immunology, Viruses, and Science China Life Sciences. He has worked as Chinese Public Health Team leader in Africa during the Ebola epidemic. During the COVID-19 pandemic, he worked onsite in difference outbreaks for the emergency responses.
Name & Affiliation:
Christopher John Vavricka
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology
Title: Towards the improvement of covalent influenza neuraminidase inhibitors
Abstract:
In 2013, our collaboration between researchers in China and Japan resulted in the first crystal structure of influenza neuraminidase (NA) in complex with a covalent inhibitor, proving the concept that covalent NA inhibitors can target influenza. Since then we have focused on the modification of the anomeric carboxy group of sialic acid analogues to stabilize the covalent bond that is formed with the NA catalytic tyrosine. This has resulted in the design and synthesis of anomeric phosphonate and sulfonate analogues of sialic acid, with potential for more potent covalent influenza NA inhibition.
Biography:
Christopher John Vavricka Jr. completed his Ph.D. in Biochemistry under Professor Jianyong Li at the Virginia Tech Department of Biochemistry. As a postdoctoral researcher, he worked on the structure-based development of neuraminidase inhibitors, in the laboratory of Professor George F. Gao at Chinese Academy of Sciences Institute of Microbiology. Chris moved to the laboratory of Professor Hiromasa Kiyota at Okayama University to work on the organic synthesis of novel sialic acid analogues as inhibitors of neuraminidase. His experience in enzymology and medicinal chemistry was then combined to engineer the microbial production of medicinal compounds at Kobe University. In December 2022 Chris established the Medicinal Enzyme Engineering Laboratory at the Department of Biotechnology and life Science, Tokyo University of Agriculture and Technology.
Name & Affiliation:
Yohei Watanabe
Department of Infectious Diseases, Kyoto Prefectural University of Medicine
Title: Stimulation of IFN-b responses by aberrant SARS-CoV-2 small viral RNAs acting as RIG-I agonists
Abstract:
Patients with severe COVID-19, caused by SARS-CoV-2, experience a cytokine storm, which is characterized by increased cytokine levels across disease stages, but a delayed IFN response. To date, the mechanisms driving this characteristic IFN-b induction are poorly understood. To address this, we deep-sequenced small viral RNAs in a variety of human cells and Vero cells infected with SARS-CoV-2 (Wuhan strain, delta, omicron BA.1 and BA.2 variants) and two endemic human CoVs (HCoVs) 229E and OC43 for comparison, and discovered that SARS-CoV-2-infected cells accumulate large amounts of small viral RNAs (svRNAs) which act as potent RIG-I ligands that stimulate a delayed, then over-exuberant, IFN-b response, as observed in severe COVID-19. Remarkably, a large majority of svRNAs encoded the exact 5′ end of the positive-sense genome and the first 60-nt end forming duplex structures and bearing 5′-triphosphates are responsible for this immune stimulatory ability. The 5′ end svRNAs were also produced in the lungs of infected hamsters in vivo and reconstituted human airway epithelia ex vivo. We propose that RIG-I activation by accumulated 5′ end svRNAs overcomes the IFN-antagonistic ability of other viral proteins and drives IFN production in later stage of infection. We also propose that this stoichiometric imbalance contributes to disease development in severe COVID-19.
Biography:
Dr. Watanabe is an associate professor at the Graduate School of Medical Sciences, Kyoto Prefectural University of Medicine, Japan. His research interests include evolutionary dynamics of zoonotic viruses at virus-host interface, including community, individual and cellular levels. He has characterized adaptation dynamics of H5N1 and H9N2 influenza viruses in infected patients and human airway cells. Recently, he has been also researching the mechanism by which SARS-CoV-2 causes severe illness.
Name & Affiliation:
Jianqing Xu
Institutes of Biomedical Sciences, Fudan University
Institutes of Biomedical Sciences, Fudan University
Title: Establishing/Boosting Mucosal Immunity by Mucosal Inoculation of Vaccine in Addition to Routinely Muscular Immunization
Abstract:
Mucosa is an interface primarily attacked by a number of pathogens, establishment or enhancement of mucosal immunity will protect host from invasion at the first line, thereby may improve the efficacy to abort infection. However, it remains to be expored how to optimize the vaccination strategy to establish or boost mucosal immune responses.
We dissected the protective immune mechanism in H7N9-infected patients, and observed that H7N9-specific T-cell responses played an crucial role in early recovery whereas neutralization antibodies engaged in protection and recovery later. Vigorous T-cell reponses could appear as early as day 7 after infection, earlier development of T-cell responses correlates with earlier release from hospitalization; The delay to elicit T-cell responses will prolong disease manifectations, and further involement of neutralization antibody will be necessary.
To determine how and where T cells exert their roles, we employed vaccination model to establish systemic or systemic plus mucosal T-cell immune responses and then challenged with mucosal attack of influenza virus, importantly systemic T-cell responses alone are unable or only partially to protect the immunized animals, mucosal T-cell responses is necessary for fully protection.Importantly, the mucosal inoculation in addition to muscular immunization enhances mucosal T-cell responses; Indeed neutralization anbodies is also enhanced through mucosal vaccination. Interestingly, rectal mucosal T-cell responses is only boosted by an intrarectal inoculation at rectal mucosal site.
We dissected the protective immune mechanism in H7N9-infected patients, and observed that H7N9-specific T-cell responses played an crucial role in early recovery whereas neutralization antibodies engaged in protection and recovery later. Vigorous T-cell reponses could appear as early as day 7 after infection, earlier development of T-cell responses correlates with earlier release from hospitalization; The delay to elicit T-cell responses will prolong disease manifectations, and further involement of neutralization antibody will be necessary.
To determine how and where T cells exert their roles, we employed vaccination model to establish systemic or systemic plus mucosal T-cell immune responses and then challenged with mucosal attack of influenza virus, importantly systemic T-cell responses alone are unable or only partially to protect the immunized animals, mucosal T-cell responses is necessary for fully protection.Importantly, the mucosal inoculation in addition to muscular immunization enhances mucosal T-cell responses; Indeed neutralization anbodies is also enhanced through mucosal vaccination. Interestingly, rectal mucosal T-cell responses is only boosted by an intrarectal inoculation at rectal mucosal site.
Biography:
Dr. Jianqing Xu graduated from China Medical University with bachelor’s and master’s degree, received his Ph.D. in Microbiology from Peking Union Medical College (1997), and pursued his postdoctoral research in Research Institute for Genetic and Human Therapy affiliated to Georgetown University and appointed as Research Assistant professor at Department of Microbiology and Immunology in 2001. He then joined in China CDC HIV/AIDS Center as Principal Investigator in 2004. Four years later, he moved to Fudan University to take a professorship position and became tenured professor in Fudan University in 2014.
Name & Affiliation:
Philip Man-Lung Yeung
Department of Microbiology, The University of Hong Kong
Department of Microbiology, The University of Hong Kong
Title: Development of a novel animal model for studying enterovirus infection
Abstract:
Enterovirus D68 (EV-D68) is a reemerging pathogen, which causes severe respiratory symptoms globally. EV-D68 usually causes mild to severe flu-like respiratory illness in children, but mild or no symptom in adults. Currently, there is no specific treatment or vaccine for EV-D68 infection. Numerous mouse models were established to investigate EV-D68 respiratory and neurological diseases. Diseases were developed either in neonatal mice or immunocompetent adult mice after virus inoculation. However, neither of the model reflects actual infection scenario in human. Respiratory and neurological diseases not only are found in children or immunecompromised people, but also in healthy adults. An alternative mice model is required to bypass such limitations and mimic authentic disease progression. Thus, a transgenic mouse model was constructed by introducing human tryptophanyl-tRNA synthetase (hWARS) gene into the mouse genome. In our study, EV-D68 infected both neonatal and adult mice causing limb paralysis. Our study established a platform to study EV-D68 pathogenesis and evaluate candidate treatments or vaccines.
Biography:
Dr. Yeung is an Associate Professor at HKU’s Department of Microbiology. His primary research area involves the use of cutting-edge technology platforms to investigate the molecular pathogenesis and host-virus interaction of human pathogenic viruses. Dr. Yeung’s research has consistently yielded high-quality results, which have been published in many prestigious international journals.
One of his recent notable contributions, published in Cell, involves the discovery of a novel cell entry mechanism of SARS-CoV-2. This mechanism involves the interaction of the virus with soluble ACE2. Additionally, Dr. Yeung’s work on enterovirus has led to the identification of a novel cellular entry factor, hWARS. This discovery has significantly improved our understanding of how enterovirus establishes productive infections. These breakthroughs are expected to advance the field significantly.
In addition to his research, Dr. Yeung actively participates in various scientific communities, including the Institute of Biomedical Science, American Society for Microbiology, and Society of Chinese Bioscientists in America, among others. He also serves in editorial capacities for several international peer-reviewed journals.
One of his recent notable contributions, published in Cell, involves the discovery of a novel cell entry mechanism of SARS-CoV-2. This mechanism involves the interaction of the virus with soluble ACE2. Additionally, Dr. Yeung’s work on enterovirus has led to the identification of a novel cellular entry factor, hWARS. This discovery has significantly improved our understanding of how enterovirus establishes productive infections. These breakthroughs are expected to advance the field significantly.
In addition to his research, Dr. Yeung actively participates in various scientific communities, including the Institute of Biomedical Science, American Society for Microbiology, and Society of Chinese Bioscientists in America, among others. He also serves in editorial capacities for several international peer-reviewed journals.
Name & Affiliation:
Jane Jie Zhou
Department of Microbiology, The University of Hong Kong
Department of Microbiology, The University of Hong Kong
Title: Establishing respiratory organoids for studying virus-host interaction
Abstract:
Conventionally, in vitro studies of human biology and pathology, including virus-host interaction, have hinged on the immortalized and cancer-derived cell lines that comprise homogenous clonal cells. These cell lines can barely model native human epithelia composed of multiple cell populations. We derive organoids from primary lung tissues and nasal cells highly efficiently, which provide a stable and self-renewable source for long-term expansion. We then induce differentiation in the long-term expandable organoids and generate mature nasal, airway and alveolar organoids that morphologically and functionally phenocopy the human respiratory epithelium. Namely, we have established the first adult stem cell-derived respiratory organoid culture system that enables scientists to rebuild and expand the entire human respiratory epithelium in culture plates with super efficiency and stability. We demonstrate that these respiratory organoids are robust and biologically active tools for assessing human susceptibility to emerging respiratory viruses.
Biography:
Dr. Jie Zhou’s research interests primarily focus on the establishment of organoids for studying virus-host interactions. Notably, her team has achieved groundbreaking milestones in this field, including the establishment of the first adult stem cell-derived respiratory organoid culture system and the first bat intestinal organoids. These physiologically active organoids make them ideal in vitro models for virus research. They are particularly valuable for modeling viral infections and investigating virus-host interactions.
Dr. Zhou earned her PhD in the Department of Microbiology HKU in 2007. Following her postdoctoral training at UCSF, she joined the department in 2009. Throughout her research career, she has published over 100 research papers, which have garnered more than 8000 citations. Her significant contributions have also earned her recognition as a Clarivate Analytics Essential Science Indicators (ESI) Top 1% highly cited Scholar since 2021.
Dr. Zhou earned her PhD in the Department of Microbiology HKU in 2007. Following her postdoctoral training at UCSF, she joined the department in 2009. Throughout her research career, she has published over 100 research papers, which have garnered more than 8000 citations. Her significant contributions have also earned her recognition as a Clarivate Analytics Essential Science Indicators (ESI) Top 1% highly cited Scholar since 2021.
Name & Affiliation:
Fengcai Zhu
Jiangsu Provincial Center for Disease Control and Prevention
Jiangsu Provincial Center for Disease Control and Prevention
Title: Chinese Vaccine Innovation and Emergency trial
Abstract:
In recent years, we mainly conducted 7 vaccines’ clinical trials, including 2 imported registered vaccines, 3 emergency vaccines, and 2 innovative vaccines. During these series of works, we established an early identification method of the optimal immunization schedule with reverse cumulative curve, presided over the world’s largest cohort trial of Hepatitis E vaccine. Also, we confirmed EV71 vaccine immunological surrogate endpoint for accurate and rapid evaluation, used hierarchical endpoints in EV71 vaccine clinical trials to comprehensively evaluate the protective efficacy of the vaccine, and found the efficacy of EV71 vaccine showed an inverted pyramid.Since 2020, our team completed more than 30 clinical trials of COVID-19 vaccines in China, which covering all five technical platforms for COVID-19 vaccine development.We launched first clinical study of heterologous prime-boost immunization and found that the levels of immunity responses induced by heterologous prime-boost immunization were higher than homologous vaccination. In 2021, our team conducted two clinical trials for mucosal immunization vaccines. Mucosal immunization can be administered through two main routes: nasal and respiratory tract/lung inhalation. The level of neutralizing antibodies induced by aerosolized Ad5-nCoV heterologous prime-boost immunization is the highest among the different COVID-19 vaccines reported globally. In the future, we hope to discover the better vaccine combinations through an adaptive design platform.
Biography:
Feng-Cai Zhu is the expert of Clinical vaccinology, the deputy Director of Jiangsu Provincial Center for Disease Control and Prevention, Member of WHO Expert Group on COVID-19 Vaccine Priority. He is also the President of Vaccine Clinical Research Sub-group in China Association for vaccines, the President of Vaccine Clinical Research Committee in Chinese Preventive Medicine Association, the Expert of National Drug Review, and Member of the first National Immunization Programme Expert Advisory Committee. He was awarded the “Special Government allowance” of The State Council, the first level qualified personnel in Jiangsu province “333 project” , and he was selected into the National People’s Ten Thousand Talents Program. Lancet Perspective: Feng-Cai Zhu, leading vaccine evaluation in China. He presided over the national science and technology major projects, “863” project, and National Natural Science Foundation; won 7 provincial and ministerial science and technology awards, including 2 first prizes of Jiangsu Science and Technology Awards. He has published 20 original articles in N Engl J Med、Lancet、Nat Med、Lancet Respir Med、Lancet Infect Dis as the first or corresponding author, of which 3 in NEJM and 7 in Lancet, and 11 were ESI highly cited papers.