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

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Moore, SC ORCID: 0000-0001-8610-2806, Kronsteiner, B, Longet, S, Adele, S, Deeks, AS, Liu, C, Dejnirattisai, W, Reyes, LS, Meardon, N, Faustini, S et al (show 54 more authors) , Al-Taei, S, Tipton, T, Hering, LM ORCID: 0000-0002-5736-8725, Angyal, A, Brown, R, Nicols, AR, Dobson, SL ORCID: 0000-0002-4958-0021, 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 ORCID: 0000-0002-5903-3881, 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 and Turtle, L ORCID: 0000-0002-0778-1693 (2023) Evolution of long-term vaccine-induced and hybrid immunity in healthcare workers after different COVID-19 vaccine regimens Med, 4 (3). 191-215.e9. ISSN 2666-6359, 2666-6340

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	PITCH Consortium, Humans, Vaccines, Prospective Studies, Health Personnel, Immunity, Humoral, Antibodies, Neutralizing, COVID-19, SARS-CoV-2, COVID-19 Vaccines, BNT162 Vaccine, ChAdOx1 nCoV-19
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences Faculty of Health & Life Sciences > Inst. Infection, Vet & Ecological Sciences
Depositing User:	Symplectic Admin
Date Deposited:	17 May 2023 14:07
Last Modified:	24 Jan 2026 04:07
DOI:	10.1016/j.medj.2023.02.004
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3170447
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