Toggle Main Menu Toggle Search

Open Access padlockePrints

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

Lookup NU author(s): Alex Nicols, Jess Tyerman, Dr Rebecca PayneORCiD, Dr Christopher DuncanORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2023Background: 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.

Publication metadata

Author(s): 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

Publication type: Article

Publication status: Published

Journal: Med

Year: 2023

Volume: 4

Issue: 3

Pages: 191-215.e9

Print publication date: 10/03/2023

Online publication date: 15/02/2023

Acceptance date: 10/02/2023

Date deposited: 28/06/2023

ISSN (print): 2666-6359

ISSN (electronic): 2666-6340

Publisher: Cell Press


DOI: 10.1016/j.medj.2023.02.004

PubMed id: 36863347


Altmetrics provided by Altmetric


Funder referenceFunder name
204721/Z/16/ZWellcome Trust
211153/Z/18/ZWellcome Trust
Alder Hey Charity
Centre of Excellence in Infectious Diseases Research (CEIDR)
Chinese Academy of Medical Sciences (CAMS)
Francis Crick Institute
Schmidt Futures
nnovation Fund for Medical Science (CIFMS), China
Oak Foundation
Red Avenue Foundation
UK Department of Health and Social Care
Wellcome Trust