Completed Infection & Immunity Pregnancy, Children & Inherited Conditions

Investigation of pre-existing immunity to coronaviruses; implications for immunopathology and pathophysiology of COVID-19 disease

Funder Wellcome/DFID Charity-funded
Recipient organisation University of Oxford Source-published name: The University of Oxford
Funding £1.3M
Period Apr 2020 — Jun 2022

In plain English

AI plain-English summary

A prior infection with a common cold coronavirus could, in some cases, make a subsequent COVID-19 infection worse rather than protecting against it. This project addresses a critical blind spot in pandemic response: we do not know whether pre-existing antibodies against mild, seasonal coronaviruses (229E, NL63, OC43, HKU1) can trigger antibody-dependent enhancement (ADE)—a process where non-neutralising antibodies actually help the virus enter cells, increasing viral load and disease severity. ADE was observed in animal models after some SARS vaccines, raising concerns that the same mechanism could undermine COVID-19 vaccine development. The researchers will perform detailed systems serology on blood samples from children and adults in the UK and Africa, mapping cross-reactive immune responses between common and highly pathogenic coronaviruses (SARS-CoV-2, SARS, MERS). If this research succeeds, it will directly inform vaccine design—flagging which antibody profiles are safe and which risk exacerbating disease. This is fundamental science with immediate practical stakes: without this knowledge, a vaccine could inadvertently prime the immune system for harm instead of protection.

View original technical description
Background; It is unknown how prior exposure to commonly circulating human coronaviruses (HCoV) impacts immunity against highly-pathogenic species (SARS, SARS-CoV-2 & MERS). There are limited data, across Europe, Asia and Africa, on the prevalence of infection and seroconversion against widely circulating and mildly symptomatic HCoVs (229E, NL63, OC43, and HKU1). There is a current supposition that antibody-dependent-enhancement (ADE) may play a role in the pathophysiology of COVID-19. ADE occurs when non-neutralizing antiviral proteins facilitate virus entry into host cells, leading to increased infectivity in the cells. In such cases, higher viremia has been measured and the clinical course of disease can be more severe. In preclinical animal models, immunopathology was observed after challenge following vaccination with some SARS vaccines. Therefore, concerns have been raised regarding the impact of immunopathology and ADE on prophylactic vaccination against SARS and possibly SARS-CoV-2. Goals: to perform detailed systems serology of pre-existing immunity, in children and adults, from the UK and Africa, towards novel and commonly circulating coronaviruses. Impact: These studies highlight the limited knowledge in the field and a need for a systematic approach to investigate cross-reactive humoral immunity against HCoV to inform the immunopathology and pathophysiology of COVID-19.

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Researchers

Teresa Lambe (EPMC Awardee)

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Original classification

Research Grant

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