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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.