Third exposure to COVID-19 infection or vaccination differentially impacts T cell responses.
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Ahimbisibwe Gift, Greenwood David, Wilkinson Katalin Andrea, Gahir Joshua, Townsley Hermaleigh, Miah Murad, Bawumia Philip, Chaloner Charlotte, Levi Dina, Hobson Philip, Riddell Andy, Hobbs Agnieszka, Dowgier Giulia, Penn Rebecca, Sanderson Theo, Stevenson-Leggett Phoebe, Daley Odiesia, Bazire James, Harvey Ruth, Fowler Ashley S, Smith Callie, Miranda Mauro, O'Reilly Nicola, Warchal Scott, Ambrose Karen, Strange Amy, Kelly Gavin, Kjar Svend, Legacy Investigators, Williams Bryan, Libri Vincenzo, Gamblin Steve, Gandhi Sonia, Swanton Charles, Bauer David Lv, Wilkinson Robert John, Carr Edward J, Wall Emma C
Аннотация
OBJECTIVE: To compare how the third exposure through mRNA booster or SARS-CoV-2 infection shapes humoral and cellular immunity following two vaccine doses.
METHODS: We compared immune responses after the third exposure in healthy adults enrolled in the UCLH-Crick Legacy cohort study (NCT04750356) between those receiving ancestral spike-encoded mRNA booster (vaccine immunity, n = 38) or COVID-19 infection (hybrid immunity, n = 13) following two vaccine doses. Immune profiles were evaluated using live virus neutralization assays, IFN-γ ELISpot, Luminex assay, flow cytometry and mass cytometry.
RESULTS: Both total anti-Spike IgG and variant-specific neutralising antibodies were comparable following infection or vaccine as a third exposure. Overall, T cell populations were similar but functionally different. CD8⁺ Effector Memory (TEM) cells in the vaccine group showed higher expression of CD69 and Granzyme B following stimulation with SARS-CoV-2 Spike peptides. In contrast, the hybrid group produced higher levels of innate immune associated cytokines IL-10 and IL-34, as well as the T cell homing chemokine CCL25, after stimulation.
CONCLUSIONS: While both exposures generated comparable breadth of protection against SARS-CoV-2 variants, our findings suggest that the route of third exposure influences different aspects of the immune response, warranting further investigation into long-term immunity at both systemic and mucosal sites.