Evolution of long-term vaccine-induced and hybrid immunity in healthcare workers after different COVID-19 vaccine regimens.
Moore SC., Kronsteiner B., Longet S., Adele S., Deeks AS., Liu C., Dejnirattisai W., Reyes LS., Meardon N., Faustini S., Al-Taei S., Tipton T., Hering LM., Angyal A., Brown R., Nicols AR., Dobson SL., Supasa P., Tuekprakhon A., Cross A., Tyerman JK., Hornsby H., Grouneva I., Plowright M., Zhang P., Newman TAH., Nell JM., Abraham P., Ali M., Malone T., Neale I., Phillips E., Wilson JD., Murray SM., Zewdie M., Shields A., Horner EC., Booth LH., Stafford L., Bibi S., Wootton DG., Mentzer AJ., Conlon CP., Jeffery K., Matthews PC., Pollard AJ., Brown A., Rowland-Jones SL., Mongkolsapaya J., Payne RP., Dold C., Lambe T., Thaventhiran JED., Screaton G., Barnes E., Hopkins S., Hall V., Duncan CJA., Richter A., Carroll M., de Silva TI., Klenerman P., Dunachie S., Turtle L., PITCH Consortium None.
BACKGROUND: Both infection and vaccination, alone or in combination, generate antibody and T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the maintenance of such responses-and hence protection from disease-requires careful characterization. In a large prospective study of UK healthcare workers (HCWs) (Protective Immunity from T Cells in Healthcare Workers [PITCH], within the larger SARS-CoV-2 Immunity and Reinfection Evaluation [SIREN] study), we previously observed that prior infection strongly affected subsequent cellular and humoral immunity induced after long and short dosing intervals of BNT162b2 (Pfizer/BioNTech) vaccination. METHODS: Here, we report longer follow-up of 684 HCWs in this cohort over 6-9 months following two doses of BNT162b2 or AZD1222 (Oxford/AstraZeneca) vaccination and up to 6 months following a subsequent mRNA booster vaccination. FINDINGS: We make three observations: first, the dynamics of humoral and cellular responses differ; binding and neutralizing antibodies declined, whereas T and memory B cell responses were maintained after the second vaccine dose. Second, vaccine boosting restored immunoglobulin (Ig) G levels; broadened neutralizing activity against variants of concern, including Omicron BA.1, BA.2, and BA.5; and boosted T cell responses above the 6-month level after dose 2. Third, prior infection maintained its impact driving larger and broader T cell responses compared with never-infected people, a feature maintained until 6 months after the third dose. CONCLUSIONS: Broadly cross-reactive T cell responses are well maintained over time-especially in those with combined vaccine and infection-induced immunity ("hybrid" immunity)-and may contribute to continued protection against severe disease. FUNDING: Department for Health and Social Care, Medical Research Council.