Research News

17 Jun 2019

Preventing an Antigenically Disruptive Mutation in Egg-Based H3N2 Seasonal Influenza Vaccines by Mutational Incompatibility

Chris Mok, team leader at HKU-Pasteur, and Tomas Lyu, research assistant, just signed a major publication in Cell Host & Microbe with Professor Ian Wilson, Scripps Research, and Nicholas Wu, Scripps Research and 2017 HKU-Pasteur Virology Course alumnus: 
Chris Mok and Ian Wilson, who co-led the study, have found that a mutation called G186V could be a useful addition to the H3N2 influenza vaccine. Preparing a seasonal flu vaccine with the G186V mutation may prevent a vexing problem that commonly occurs during the vaccine manufacturing process.
Egg-based seasonal influenza vaccines are the major preventive countermeasure against influenza virus. However, their effectiveness can be compromised when antigenic changes arise from egg-adaptive mutations on influenza hemagglutinin (HA). The L194P mutation is commonly observed in egg-based H3N2 vaccine seed strains and significantly alters HA antigenicity. An approach to prevent L194P would therefore be beneficial. We show that emergence of L194P during egg passaging can be impeded by preexistence of a G186V mutation, revealing strong incompatibility between these mutations. X-ray structures illustrate that individual G186V and L194P mutations have opposing effects on the HA receptor-binding site (RBS), and when both G186V and L194P are present, the RBS is severely disrupted. Importantly, wild-type HA antigenicity is maintained with G186V, but not L194P. Our results demonstrate that these epistatic interactions can be used to prevent the emergence of mutations that adversely alter antigenicity during egg adaptation.
Authors: Wu NC, Lv H, Thompson AJ, Wu DC, Ng WWS, Kadam RU, Lin CW, Nycholat CM, McBride R, Liang W, Paulson JC, Mok CKP, Wilson IA (2019)
Cell Host Microbe pii: S1931-3128(19)30216-1. doi: 10.1016/j.chom.2019.04.013.
Chris Mok, team leader at HKU-Pasteur, and Tomas Lyu, research assistant

14 Jun 2019

[Seminar] Cryptic transmission risk factors in HIV transmission networks by Manon Ragonnet

Manon Ragonnet, MRC Fellow, Imperial College London will give a talk at HKU-Pasteur on July 9, 2019 about Cryptic transmission risk factors in HIV transmission networks:

Date: 9 July 2019
Time: 16:00 - 17:30
Venue: HRI-1B, Ground Floor, HKJC Building for Interdisciplinary Research 5 Sassoon Road, Pokfulam, Hong Kong
HIV combination antiretroviral therapy prolongs the lives of people living with HIV and significantly reduces onward transmission. Yet, HIV continues to spread through increasingly concentrated populations and poorly understood contact networks. The UK and the USA have accumulated large datasets of HIV sequences from patients and anonymised genetic analysis of these sequences can elucidate transmission patterns within and between key risk groups.
In the UK, these analyses have highlighted the existence of a group of men who self-report as hete- rosexual but whose viruses link only to men who have sex with men. Further inquiry into the posi- tion of these men in reconstructed networks suggests that their behaviour may differ from that of both heterosexual men and men who have sex with men.
In Los Angeles County, California, we specifically looked at the position of transgender women (individuals assigned the male sex at birth, but who identify as women) in HIV transmission networks and developed a framework for increasing diagnosis rates among transgender women based on network structure.
Our results provide a more thorough understanding of local HIV transmission dynamics with the aim of improving targeted HIV intervention strategies.
Manon Ragonnet is a Research Fellow at Imperial College London. She studies the evolution and spread of RNA viruses (mostly HIV with a little hepatis C) using phylodynamic analysis. Her research interests stem from both the challenge presented by HIV’s formidable adaptive capacity and its public health implications. She has previously worked on HIV transmission in Canada, the US, Uganda, and South Africa and currently works in the UK and Botswana. Her current research focuses on estimating meaningful epidemic parameters during HIV outbreaks (such as the recent HIV out- break among people who inject drugs in Glasgow) and on quantifying the impact of imports into regional epidemics.

13 Jun 2019

[Seminar] Nutrition and Endemic/Emerging Infectious Diseases in Cambodia by Erik Karlsson

Erik Karlsson, Virology Unit Institut Pasteur - Cambodia, will be in Hong Kong on July the 3rd to give a lecture called Nutrition and Endemic/Emerging Infectious Diseases in Cambodia:
Date: Wednesday, 3rd July 2019
Time: 11:00 am
Venue: Seminar Room 2 (HRI-S2), Ground Floor, HKJC Building for Interdisciplinary Research, 5 Sassoon Road, Pokfulam, Hong Kong
Cambodia is a hotspot of emerging and endemic infectious disease. In addition, after facing numerous years of rampant undernutrition, Cambodia is now facing a “triple burden” of malnutrition where obesity and under weight exist side-by-side with other dietary concerns, such as micronutrient deficiency. This talk will explore the current status of both infectious disease and nutrition in Cambodia and discuss some of the work done on understanding the interplay between nutrition and several pathogens (avian and seasonal influenza, dengue, rabies) in the context of disease severity, transmission, vaccination, and viral evolution itself.
Dr. Karlsson obtained his doctoral degree in Nutrition from the University of North Carolina at Chapel Hill, Gilling’s School of Global Public Health and was a postdoc at St. Jude Children’s Research Hospital where his work focused on nutritional influences on influenza virus pathogenesis and global influenza sur veillance. He currently ser ves as the Senior Research Fellow in the Virology Unit at Institut Pasteur du Cambodge (IPC) in Phnom Penh, Cambodia. His work covers several aspects of virus research in Cambodia including surveillance and vaccination, with a special interest in the interplay between malnutrition and infection.

03 Jun 2019

Theme-based Research Scheme seminars with Sophie Valkenburg and (HKU-Pasteur) and Katherine Kedzierska (University of Melbourne, The Peter Doherty Institute)

Sophie Valkenburg, team leader at HKU-Pasteur, and Katherine Kedzierska, Department of Microbiology & Immunology, University of Melbourne, The Peter Doherty Institute for Infection & Immunity, will give seminars as part of the Theme-based Research Scheme on Viral, Host and Environmental Determinants of Influenza Virus Transmission and Pathogenesis. 

Date: 12 June 2019 (Wed)
Time:  11:00-12:30
Venue: Seminar Room 3, G/F The HKJC Bldg for Interdisciplinary Research
5 Sassoon Road, HK 
>>> Immune correlates in influenza vaccination and infection
By Dr Sophie Valkenburg
Inactivated influenza vaccines (IIV) are the most widely used vaccines in the world due to seasonal epidemics and annual updates to vaccine strains. These vaccines account for over 500 million doses costing over $5 billion USD. Older adults experience the highest mortality and are prioritised for seasonal vaccination yet can have the lowest vaccine efficacy. What happens to our immune system when we are repeatedly vaccinated for influenza, and which vaccine is the best option?
The only standardised and widely accepted immune correlate of protection for influenza vaccine mediated protection is, Haemagglutinin inhibition antibodies (HAI). Yet HAI gives an incomplete picture to vaccine responses and their immunogenicity, whilst next generation influenza vaccines need alternate protective immune correlates defined. In a randomised control immunogenicity trial of older adults, in close collaboration with the CDC and Professor Ben Cowling’s team, we are deciphering immune correlates for repeated and enhanced vaccines in older adults in Hong Kong. Our focus is vaccine immunogenicity for antibody quality and cellular responses.
We recently reported that one round of twice-annual vaccination resulted in elevated HAI titers in the second round of vaccination, but reduced H3N2-specific influenza-specific CD4+ T cell responses. In further studies we have assessed vaccination effects on recruitment of T follicular helper cell and plasma blast B cell responses, which are important drivers for high quality antibody responses. We further characterised influenza-specific antibody quality by IgG sub-classes associated with ADCC effector functions. Enhanced influenza vaccines were also assessed in a mouse model of vaccination and lethal influenza challenge to determine vaccine superiority. We found a particular advantage for adjuvanted influenza vaccines for both antibodies and cellular responses in the mouse model.
>>> Universal CD8+T Cell Immunity to Influenza Viruses
By Professor Katherine Kedzierska
Professor Kedzierska’s research is centered on understanding key factors driving generation of optimal immunity in viral infections, especially pandemic, seasonal and newly emerged influenza viruses such as A/H7N9. Her work spans basic research from mouse experiments to human immunity, through to clinical settings, with a particular focus on understanding universal cross-strain protective T cell immunity to influenza viruses. Her studies aim to identify key correlates of severe and fatal influenza disease in high-risk groups, including young children, the elderly and Indigenous Australians.