Can cross-protective airway-resident immunity be harnessed for SARS-CoV-2 variant protection in UK and Malawian populations with or without HIV infection?
Year of award: 2022
Grantholders
Dr Mariana Diniz
University College London, United Kingdom
Dr Rhona Mijumbi-Deve
Liverpool School of Tropical Medicine, United Kingdom
Dr Henry Mwandumba
Malawi Liverpool Wellcome Trust Clinical Research Programme, Malawi
Dr Elena Mitsi
Liverpool School of Tropical Medicine, United Kingdom
Dr Kondwani Jambo
Liverpool School of Tropical Medicine, United Kingdom
Prof Mala Maini
University College London, United Kingdom
Prof Daniela Ferreira
University of Oxford, United Kingdom
Project summary
Coinciding with >70% seroprevalence in Malawi and >75% vaccination coverage in the UK, the omicron variant has had lower mortality than the delta variant. Both prior infection and vaccination protect against severe COVID-19, and vaccination combined with infection induces highly cross-reactive hybrid immunity. Pre-existing cross-reactive T cells targeting highly conserved replication proteins abort SARS-CoV-2 infection before PCR positivity or antibody seroconversion, leading to protection against COVID-19. Our unpublished data suggest that this rapid immune-surveillance is attributable to pre-existing cross-reactive SARS-CoV-2 T cells that are highly enriched in the human airways. Furthermore, lung-resident B cells elicit antibodies that cross-neutralise influenza variants and recent work has highlighted the protective potential of mucosal IgA against COVID-19. These data suggest that cross-reactive airway immune responses could be critical in defence against emerging variants. We hypothesise that airway-compartmentalised T and B cells provide an enriched long-lived reservoir of cross-reactive immunity against emerging variants than can protect against COVID-19, and we postulate that is impacted by background exposure, vaccination status and pre-existing HIV infection, in Malawi and UK adults. An understanding of tissue-resident long-lived, broadly cross-reactive immunity is vital for development of next generation mucosal-targeted vaccines and for future studies predicting susceptibility to novel variants.