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.
Our 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.