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Evolution of long-term vaccine-induced and hybrid immunity in healthcare workers after different COVID-19 vaccine regimens.

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Moore, Shona C 
Kronsteiner, Barbara 
Longet, Stephanie 
Adele, Sandra 
Deeks, Alexandra S 


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.



COVID vaccine, COVID-19, SARS-CoV-2, T cells, Translation to population health, antibody, immunity, Humans, COVID-19 Vaccines, BNT162 Vaccine, ChAdOx1 nCoV-19, Prospective Studies, COVID-19, SARS-CoV-2, Vaccines, Antibodies, Neutralizing, Health Personnel, Immunity, Humoral

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Elsevier BV
National Institute for Health Research (NIHR) (NIHR300669, NIHR203792, NIHR300791)
Wellcome Trust (090532/Z/09/Z, 205228/Z/16/Z, 110058/Z/15/Z)
The Francis Crick Institute (CC2223)