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30 Jul 2021

SARS-CoV-2 Specific T Cell Responses Are Lower In Children And Increase With Age And Time After Infection

Sophie Valkenburg and her team sign a major publication in Nature Communications, with Leo Poon and Malik Peiris, to understand the difference in SARS-CoV-2 specific T cell responses between children and adults.
 
 
Abstract
SARS-CoV-2 infection of children leads to a mild illness and the immunological differences with adults are unclear. Here, we report SARS-CoV-2 specific T cell responses in infected adults and children and find that the acute and memory CD4+ T cell responses to structural SARS-CoV-2 proteins increase with age, whereas CD8+ T cell responses increase with time post-infection. Infected children have lower CD4+ and CD8+ T cell responses to SARS-CoV-2 structural and ORF1ab proteins when compared with infected adults, comparable T cell polyfunctionality and reduced CD4+ T cell effector memory. Compared with adults, children have lower levels of antibodies to β-coronaviruses, indicating differing baseline immunity. Total T follicular helper responses are increased, whilst monocyte numbers are reduced, indicating rapid adaptive co-ordination of the T and B cell responses and differing levels of inflammation. Therefore, reduced prior β-coronavirus immunity and reduced T cell activation in children might drive milder COVID-19 pathogenesis.
 
 

19 Jul 2021

Malik Peiris Published a Study Comparing Antibody Level in BioNTech and Sinovac Vaccine Recipients

Published in the Lancet Microbe with Prof Ben Cowling and Prof Gabriel Leung, the study has found that recipients of the BioNTech Covid-19 vaccine have 10 times more antibodies than those who took Sinovac.

The study reports comparative data on SARS-CoV-2 vaccine immunogenicity in health-care workers in Hong Kong who received either the BNT162b2 vaccine (Comirnaty; Fosun–BioNTech) or the inactivated virus (vero cell) vaccine (Coronavac; Sinovac). 
 
They have collected blood samples before vaccination, before the second dose, and 21–35 days after the second dose, testing samples for antibodies to SARS-CoV-2 using an ELISA to detect antibodies that bind to the receptor binding domain of the spike protein, testing ELISA-positive samples for neutralising antibodies with a surrogate virus neutralisation (sVNT) assay, and then a plaque reduction neutralisation test (PRNT) with live SARS-CoV-2 virus.
 
 
 

13 Jul 2021

Leo Poon To Coordinate Major UGC Funded TRS 2021/2022 Project

The University Grant Council has announced the results of the Theme-based Research Scheme 2021/22 funding approval on 13 July with eight research proposals awarded total funding of $415 million.

Amongst the eight proposals, the Virological, Immunological and Epidemiological Characterization of COVID-19 project coordinated by Professor Leo Poon, Co-Director at HKU-Pasteur and Principal Investigator at the Centre for Immunology & Infection (C2i), was awarded more than HK$68 million, the highest total for this round of funding. 
 
It will help to reveal COVID-19 transmission and pathogenicity and identify vaccination strategies against SARS-CoV-2 and provide a scientific basis for developing policies and measures to control the pandemic.
 
The team includes Sophie Valkenburg (HKU-Pasteur), Hui-Ling Yen (School of Public Health, HKUMed), Michael Chan (SPH and C2i), Ben Cowling (SPH), David Hui (CUHK), Tommy Lam (SPH and C2i), Matthew McKay (HKUST), Malik Peiris (HKU and C2i) and Anderson Shum (HKU).
 
Abstract
The causative virus of COVID-19, SARS-CoV-2, is likely to become an endemic infection in humans. Mutations in the SARS-CoV-2 genome will continue to arise in the future. This multidisciplinary team will address two key COVID-19 research areas: 1) monitoring genotypic and phenotypic changes in SARS-CoV-2 and 2) investigating immune responses following natural infection or vaccination. Our project will help to reveal COVID-19 transmission and pathogenicity and identify vaccination strategies against SARS-CoV-2. Information generated from this work will be shared with relevant stakeholders in real time to inform healthcare policy. 
 
The proposed studies will leverage our well-established research program on COVID-19. The first specific aim of our study is to experimentally identify SARS-CoV-2 strains that are of public health concern (e.g., Variants of Concern). We will focus on genetic and phenotypic characterization of naturally occurring viruses using a range of in vitro and in vivo experimental models. Mutations that lead to phenotypic changes will be further confirmed by reverse genetic approaches. We will also use next generation sequencing technology to understand the virus population dynamics in a transmission chain. The second specific aim is to study COVID-19 immune responses. We will study immune responses induced by natural infection or vaccination in community cohorts and in patient cohorts. Adults and children with virologically confirmed SARS-CoV-2 infection will be followed up over 3 years for a detailed characterization of their antibody and T cell responses. These individuals will be monitored for re-infection. The quality and kinetics of immune responses triggered by COVID-19 infection or commercial COVID-19 vaccines will be assessed and compared. We will also use animal experimental models to develop and optimize vaccination strategies for enhancing the protection provided by COVID-19 vaccines against disease and transmission. Relevant viruses obtained from the first specific aim, particularly potential immune escape variants, will be used to investigate effects of viral mutations on COVID-19 immune responses. We will use bioinformatics approaches to identify potential cellular and/or serological markers that can be used as correlates for protection and viral epitopes of vaccine potential. We will use these results, together with epidemiological data, to understand COVID-19 transmission in Hong Kong and beyond.
 
 
Impact to the Research Field, Society and Economy
The COVID-19 pandemic has severely impacted our daily lives. Health systems are facing the most serious global pandemic crisis in a century, with public health systems in some countries overwhelmed. This results in different control measures to prevent the spreading of COVID-19 (e.g., working at home, social distancing, restrictions on mass gathering, suspension of in-person classes and mandatory quarantine). This pandemic also has an unprecedented impact to the global economy, including Hong Kong. The impact of COVID-19, unfortunately, will not be short-lived. As this virus only jumped into humans more than one year ago, it is expected to continue to evolve in humans to enhance its fitness and evade human immune responses. The recent emergence of variants of concern (e.g., α, β, γ and δ) has highlighted these concerns. Thus, there is an urgent need to search practical options to minimize the impact of COVID-19 to our community.
 
In this proposal, we will investigate two major areas related to COVID-19. The first research area primarily focuses on studying SARS-CoV-2 variants found in humans. We will monitor for viral genetic changes and, more importantly, assess the potential public health risk (e.g., transmissibility, vaccine escape and disease severity) caused by these genetic changes. The second research area focuses on assessing COVID-19 immune responses in the local population. Specifically, we will evaluate the potential use of COVID-19 vaccines to prevent COVID-19 infection at the individual and population levels. We will also determine the strategies of using these vaccines to protect the general community in Hong Kong, while providing critical information for making COVID-19 vaccines. 
 
Overall, our study will help to inform policy makers, public health practitioners, clinicians and biotechnology industrialists for improving COVID-19 control measures. We anticipate our work will help to address urgent questions to protect the local community and beyond (i.e., risk assessment, vaccination strategy and public communication). In addition, we expect our work will also have other impacts in the long term (identifying markers as immune correlates and second-generation vaccine development). Findings of our work will be valuable for policymaking and research. In short, we aim at using our findings to change our daily activities from “new normal” back to “real normal”.
 
 
Main Points
  • COVID-19 will become an endemic disease in humans. 
  • The virus causing COVID-19 will continue to circulate and adapt in humans. This public health concern is highlighted by the recent emergence of variants of concern.
  • This program will use state-of-the-art science to study COVID-19. There are two major focuses in this study: 1) to characterize emerging SARS-CoV-2 variants and identify variants that might have increased public health risk, and 2) to assess COVID-19 immune responses in the different populations in Hong Kong.
  • Our project will help to reveal COVID-19 transmission and pathogenicity and identify vaccination strategies against SARS-CoV-2. 
  • Our data will provide a scientific basis for developing policy and measures to control COVID-19.

11 Jun 2021

Impacts of the first wave of the COVID-19 pandemic on travel-related gut microbiome and resistome changes

Our gut microbes are sensitive to environmental changes and exposures. Travel act as a key setting in which such changes are eager to happen.

In the context of the ongoing Covid-19 pandemic, Dr Hein Min Tun and PhD student Ye Peng have published in the Journal of Travel Medicine a study informing the changes in our microbiomes related to pandemic control measures implemented for travelling since the start of the outbreak in late 2019.

Collateral effects of the pandemic control measures

Over a year into the pandemic, people around the world are facing “a devastating new normal”. The comprehensive implementation of consistent pandemic control measures such as physical distancing, universal masking, and extensive hygiene are key in the global fight against the COVID-19 pandemic.

“We don’t know yet what will be the collateral damages of these measures. Apparently, they limit us to expose ourselves to diverse microbes from the environment, consequently affect our microbiome, that are implicated in health and diseases.”

According to the research team: “long-term impacts should be monitored as these measures have been widely practiced, and we probably still need them until the end of the pandemic or perhaps until a reasonable global vaccination coverage is achieved”.

Maintaining our normal gut microbiome in the midst of a pandemic

“To fully avoid potential negative consequences from control measures, we need the population to get largely vaccinated.”

This new paper is stemming from a previous study about the role of gut microbiota in the acquisition of antimicrobial resistant bacteria during international travels also published in the Journal of Travel Medicine in March 2021.

In this previous paper, the Tun Lab reported lower richness of Actinobacteria, a bacterial phylum associated with the natural environment, predisposed travellers to higher risk of acquiring antibiotic-resistant bacteria during international travel. In this study, the team observed reduced Actinobacteria richness, along with increased resistance genes during the first wave of the pandemic.

“We need to be cautious that our guts may be more susceptible to drug-resistant bacteria during the pandemic […] But at the same time, we can also use other ways to maintain our normal gut microbiome, such as exposing to natural environments with safety measures, eating fibre-rich diets, and avoiding excessive use of microbiome disruptive products.”

Indeed, although changes are observed in gut microbiome, long-term consequences of the changes are not yet fully understood and both researchers underline that: “at this moment, we should prioritize implementing pandemic control measures over considering possible negative collateral impacts because the most important is fighting against this pandemic.”

Towards extended research on the topic

This study showed the first scientific evidence of gut microbiota changes related to pandemic control measures.

Nevertheless, the research team stresses the need for more observational evidences in a larger population. According to Dr Tun and PhD student Ye Peng, a longitudinal follow-up study on health consequences and microbiome changes is also worthy of investigation.

“We need more research. Of course, we will pursue those investigations.”

>>> Gut microbiome and resistome changes during the first wave of the COVID-19 pandemic in comparison with pre-pandemic travel-related changes

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28 May 2021

HKUMed discovers a causal link among food allergies, gut microbiota development in infancy, birth methods and mother’s ethnicity

PRESS RELEASE

Researchers from HKU-Pasteur Research Pole (HKU-PRP) at the School of Public Health, LKS Faculty of Medicine of The University of Hong Kong (HKUMed), in collaboration with their Canadian collaborators, discovered for the first time a causal link between caesarean section birth, delayed gut microbiota development (persistently low Bacteroides, high Proteobacteria and colonised with Clostridium difficile) and peanut sensitivity in infants. In addition, the effect is also found to be almost four times as more pronounced in children of Asian descent than others. The findings are now published in Gastroenterology, a leading peer-reviewed medical journal. [link to the publication].

Research methods and findings

The research team characterised the composition of gut microbiota at three or four months of age and again at one year, using next-generation sequencing (a massively parallel sequencing technology used to determine the order of nucleotides in DNA). They identified four typical trajectories for bacterial development, including one in which the infants had persistently low levels of Bacteroides. It is a type of bacteria known to be critical to immune system development perhaps through the production of sphingolipids, the key to cell development and signalling. This profile was most common in babies born by caesarean section. ‘In general, the level of Bacteroides should increase with age until it becomes adult microbiome. It is an indicator for maturation of gut microbiome in children,’ said Dr Hein M Tun, Assistant Professor of HKU-PRP of School of Public Health, HKUMed.

The infants were given skin prick tests at one and three years of age to assess their reaction to a variety of allergens, including egg, milk, soy and peanut. The babies with low Bacteroides levels were found to have a threefold increase in their risk of developing a peanut sensitivity by aged three — and the risk was eight times higher for babies born to mothers of Asian descent. In the study, 12% of children are born to Asian mothers, mainly Chinese (41.5%), and they have a higher prevalence of peanut sensitisation than Caucasian children (9.4% vs 2.4%).

The team did further mediation analysis to look for causal effects between Asian ethnicity and peanut sensitisation. ‘The analysis provided additional evidence for the causal association with early gut microbiota development that links to caesarean section,’ said Dr Tun, noting it is the first study to identify this link. 

Research significance

Despite the relatively low percentage of food allergies among children in Asia, such as Mainland China (more than 6% of children under the age of five)1 and Hong Kong (5-8%)2, the latest HKUMed findings echoed with those of previous studies that Asian children born in Western countries, including Australia, have higher rates of peanut allergy than those born in Asia3.

A multitude of pre-, peri and post-natal factors, including changes in diet, microbial exposure and environment could be the reasons behind. Increasing evidence supports the role of early-life gut microbiota in developing allergic diseases, however, ecological changes of gut microbiota during infancy in relation to, as well as its interaction with host factors in food sensitisation, remain unclear.

‘As the gut microbiota are developing in infancy so is the gut’s immune system, training the gut to react to pathogens and to be tolerant of the food that we require,’ explained Dr Tun. ‘Several factors influence microbial seeding and colonisation in early-life, mainly the method of birth, breastfeeding, exposure to antibiotics and chemical disinfectants, and having siblings and furry pets.’

The best path is to avoid caesarean birth unless it is medically necessary. Asian parents especially those living in Western countries should pay extra attention to the risk of developing Western allergic phenotypes among their children, and they are advised to keep traditional diets, avoid overuse of disinfectants, and keep furry pets. ‘According to the hygiene hypothesis, overly clean environment will hamper the development of children’s immune system and they should expose to more diverse microbes in their first three years of life to prevent from allergic diseases and asthma,’ added Dr Tun.  

[1] Renz H, Allen KJ, Sicherer SH, et al. Food allergy. Nat Rev Dis Primers 2018;4:17098.

[2] Society THKA. Pathology and Causes of Food Allergy, 2015.

[3] Wang Y, Allen KJ, Suaini NHA, et al. Asian children living in Australia have a different profile of allergy and anaphylaxis than Australian-born children: A State-wide survey. Clinical & Experimental Allergy 2018;48:1317-1324.

 

About the research team

The research was conducted by a team led by Dr Hein M Tun, Assistant Professor, HKU-PRP, School of Public Health, HKUMed. The other member of the research team from HKU-PRP was Mr Ye Peng, PhD student. Investigators from the Canadian Healthy Infant Longitudinal Development (CHILD) study were Dr Anita L Kozyrskyj, Dr Bolin Chen, Mr Theodore B Konya, Dr Nadia P Morales-Lizcano, Dr Radha Chari, Dr Catherine J Field, Dr David S Guttman, Dr Allan B Becker, Dr Piush J Mandhane, Dr Theo J Moraes, Dr Malcolm R Sears, Dr Stuart E Turvey, Dr Padmaja Subbarao, Dr Elinor Simons and Dr James A Scott.

Acknowledgements
This research was specifically funded by grant 227312 from the Canadian Institutes of Health Research Canadian Microbiome Initiative (Dr Anita L Kozyrskyj). The Canadian Institutes of Health Research and the Allergy, Genes, and Environment (AllerGen) Network of Centres of Excellence provided core support for the CHILD study. Dr Tun was funded through a Canadian Institutes of Health Research Fellowship and an Alberta Innovates Postdoctoral Fellowship in Health.

About HKU-Pasteur Research Pole
HKU-Pasteur Research Pole (HKU-PRP) is a joint laboratory of HKU and Institut Pasteur, established in 2000 with the aim to developing programmes of excellence in research and education that will generate biological knowledge and advance the understanding and treatment of infectious diseases.  HKU-PRP benefits from the outstanding scientific environment offered by the School of Public Health, HKUMed, with its significant contributions, both locally and internationally, to research on emerging viral diseases and improving health.  Moreover, HKU-PRP is part of the IP International Network, a unique model for health cooperation to further science, medicine and public health with more than 100 years of history.

http://www.hkupasteur.hku.hk/ 

Researchers from HKU-Pasteur Research Pole (HKU-PRP) at the School of Public Health, LKS Faculty of Medicine of The University of Hong Kong (HKUMed), in collaboration with their Canadian collaborators, discovered for the first time a causal link between caesarean section birth, delayed gut microbiota development (persistently low Bacteroides, high Proteobacteria and colonised with Clostridium difficile) and peanut sensitivity in infants. The effect is also found to be almost four times as more pronounced in children of Asian descent than others. From left: Dr Hein M Tun, Assistant Professor, HKU-PRP, School of Public Health, HKUMed and Mr Peng Ye, PhD student.

 

Media enquiries

LKS Faculty of Medicine, HKU

Email: medmedia@hku.hk

Download the Press Release (English).

Download the Press Release (Chinese).

11 May 2021

First Participants Vaccinated In HKU Trial To Test COVID-19 Vaccines In Healthy Adolescents

PRESS RELEASE
 
Investigators of the Department of Paediatrics and Adolescent Medicine and the School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, are now launching the COVID-19 Vaccination in Adolescents (COVA) study. 300 healthy adolescents aged 11 years or above and their parents will be offered one of the COVID-19 vaccines available in Hong Kong of their choosing. The reactogenicity and immunogenicity profile of the vaccines will be compared. The first participants have just received dose 1 of their Fosun Pharma/BioNTech BNT162b2 vaccine.
 
The COVID-19 pandemic has caused more than 100 million cases and 3 million deaths globally, and over 10,000 cases in Hong Kong. The virus may cause long COVID and multisystem inflammatory syndrome in children. Some emerging virus variants have also been found to be more infectious to teenagers. Children and adolescents under 20 years old are contagious, and infected children may spread the virus to their grandparents. The prolonged suspension of classes and social distancing have also had a negative impact on students. Therefore, children and adolescents urgently need to be immunized against COVID-19.
 
COVA will recruit 300 healthy adolescents aged 11 years or above and their parents. At the moment, the families will be offered to receive the BioNTech/Fosun BNT162b2 or SinoVac's CoronaVac. Each family can freely choose the vaccine they receive, given each family member receives the same vaccine. Participants will report adverse reactions and other adverse events following immunization, and be followed up for immunogenicity assessments and vaccine breakthrough COVID-19 over a period of 3 years. Participants are covered by the Hong Kong government’s COVID-19 vaccine indemnity fund. Recruitment is ongoing, and those interested may sign up at https://paed.hku.hk/registration/cova/ or call or WhatsApp the Department of Paediatrics and Adolescent Medicine at 5944 5961 for more details. 
 
Timely local data on the reactogenicity and immunogenicity of COVID-19 vaccines in adolescents will inform the public and the government whether the vaccines should be given to adolescents, and allow complete school reopening as soon as possible.
 
About the research team
The COVA investigators include Professor Yu-Lung Lau, Doris Zimmern Professor in Community Child Health, Chair Professor of Paediatrics, Department of Paediatrics and Adolescent Medicine, HKUMed, Professor Malik Peiris, Tam Wah Ching Professor in Medical Science, Chair Professor of Virology, Centre for Immunology & Infection, Institut Pasteur and School of Public Health, HKUMed, Professor Wing-hang Leung, Head of Department and Clinical Professor, Department of Paediatrics and Adolescent Medicine, HKUMed, Professor Wenwei Tu, Antony and Nina Chan Professor in Paediatric Immunology and Professor, Department of Paediatrics and Adolescent Medicine, HKUMed, Professor Roberto Bruzzone, Visiting Professor, School of Public Health, Centre for Immunology & Infection, HKUMed, Professor Leo Poon, Professor, School of Public Health, HKUMed; also from the Department of Paediatrics and Adolescent Medicine, HKUMed: Dr Patrick Ip, Clinical Associate Professor, Dr Pamela Lee Pui-Wah, Clinical Associate Professor, Dr Jaime Rosa Duque, Clinical Assistant Professor, Dr Gilbert T Chua, Clinical Assistant Professor, Dr Wilfred Hing-sang Wong, Senior IT Manager, Ms Sau Man Chan, Research Nurse, Dr Kai N Cheong, Honorary Clinical Assistant Professor, and Mr Daniel Leung, MBBS/PhD student.
 
About the Department of Paediatrics and Adolescent Medicine, HKU 
The Department of Paediatrics and Adolescent Medicine is a pre-eminent international paediatrics department in Asia striving for the health and well-being of children and youth. We endeavour to provide high-quality children-centred health care services to the community; produce graduates, postgraduates and paediatricians of distinction, committed to lifelong learning, integrity and professionalism; engage in both basic and clinical research of innovation and high-impact, within and across disciplines; and form alliances and partnerships in order to achieve our vision and mission. 
 
About the Centre for Immunology & Infection (C2i)
The C2i is the fruit of a long-standing partnership of more than 20 years between the LKS Faculty of Medicine of the University of Hong Kong (HKUMed) and the Institut Pasteur, two major institutions combining their expertise to establish this centre of excellence. C2i, adopts innovative strategies to identify and contain emerging infectious diseases and transform Hong Kong and the Greater Bay Area into a global hub of knowledge and research.
 
The Centre for Immunology & Infection's work is centered around four major research programs to face public health challenges and make Hong Kong a global center of excellence for precision medicine population strategies and innovative interventions targeting emerging infectious diseases. They aim to characterise immune responses to infectious agents and their components in a healthy Asian population and develop new vaccine platforms for influenza, new strategies for mosquito-borne viruses and new treatments for lethal respiratory virus infections. The C2i is led by Professor Malik Peiris (Managing Director) and Professor Roberto Bruzzone (Co-director).
 
The study is funded by the Food and Health Bureau and private donations.
 
Media enquiries
Department of Paediatrics and Adolescent Medicine, HKU
Daniel Leung (Tel: 2255 4538 | Email: dan.leung@hku.hk)
 
 

Photo of COVA study team in the community vaccination centre on May 8 2021. The COVA
study is supported by experienced paediatricians, nursing staff, clinical research assistants
and medical students at the vaccination centre.
 
 

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