Prior SARS-CoV-2 infection rescues B and T cell responses to variants after first vaccine dose

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Abstract

SARS-CoV-2 vaccine rollout has coincided with the spread of variants of concern. We investigated if single dose vaccination, with or without prior infection, confers cross protective immunity to variants. We analyzed T and B cell responses after first dose vaccination with the Pfizer/BioNTech mRNA vaccine BNT162b2 in healthcare workers (HCW) followed longitudinally, with or without prior Wuhan-Hu-1 SARS-CoV-2 infection. After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 and B.1.351. By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 and B.1.351 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Single dose vaccination with BNT162b2 in the context of prior infection with a heterologous variant substantially enhances neutralizing antibody responses against variants.

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Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Fernando P Polack, Stephen J. Thomas, Nicholas R.E. Kitchin … (2023)

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)

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Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates

Edward E Walsh, Robert W Frenck, Ann Falsey … (2021)

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, coronavirus disease 2019 (Covid-19), have spread to millions of persons worldwide. Multiple vaccine candidates are under development, but no vaccine is currently available. Interim safety and immunogenicity data about the vaccine candidate BNT162b1 in younger adults have been reported previously from trials in Germany and the United States. Methods In an ongoing, placebo-controlled, observer-blinded, dose-escalation, phase 1 trial conducted in the United States, we randomly assigned healthy adults 18 to 55 years of age and those 65 to 85 years of age to receive either placebo or one of two lipid nanoparticle–formulated, nucleoside-modified RNA vaccine candidates: BNT162b1, which encodes a secreted trimerized SARS-CoV-2 receptor–binding domain; or BNT162b2, which encodes a membrane-anchored SARS-CoV-2 full-length spike, stabilized in the prefusion conformation. The primary outcome was safety (e.g., local and systemic reactions and adverse events); immunogenicity was a secondary outcome. Trial groups were defined according to vaccine candidate, age of the participants, and vaccine dose level (10 μg, 20 μg, 30 μg, and 100 μg). In all groups but one, participants received two doses, with a 21-day interval between doses; in one group (100 μg of BNT162b1), participants received one dose. Results A total of 195 participants underwent randomization. In each of 13 groups of 15 participants, 12 participants received vaccine and 3 received placebo. BNT162b2 was associated with a lower incidence and severity of systemic reactions than BNT162b1, particularly in older adults. In both younger and older adults, the two vaccine candidates elicited similar dose-dependent SARS-CoV-2–neutralizing geometric mean titers, which were similar to or higher than the geometric mean titer of a panel of SARS-CoV-2 convalescent serum samples. Conclusions The safety and immunogenicity data from this U.S. phase 1 trial of two vaccine candidates in younger and older adults, added to earlier interim safety and immunogenicity data regarding BNT162b1 in younger adults from trials in Germany and the United States, support the selection of BNT162b2 for advancement to a pivotal phase 2–3 safety and efficacy evaluation. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)

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COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T-cell responses

Ugur Sahin, Alexander Muik, Evelyna Derhovanessian … (2020)

An effective vaccine is needed to halt the spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. Recently, we reported safety, tolerability and antibody response data from an ongoing placebo-controlled, observer-blinded phase I/II coronavirus disease 2019 (COVID-19) vaccine trial with BNT162b1, a lipid nanoparticle-formulated nucleoside-modified mRNA that encodes the receptor binding domain (RBD) of the SARS-CoV-2 spike protein1. Here we present antibody and T cell responses after vaccination with BNT162b1 from a second, non-randomized open-label phase I/II trial in healthy adults, 18-55 years of age. Two doses of 1-50 μg of BNT162b1 elicited robust CD4+ and CD8+ T cell responses and strong antibody responses, with RBD-binding IgG concentrations clearly above those seen in serum from a cohort of individuals who had recovered from COVID-19. Geometric mean titres of SARS-CoV-2 serum-neutralizing antibodies on day 43 were 0.7-fold (1-μg dose) to 3.5-fold (50-μg dose) those of the recovered individuals. Immune sera broadly neutralized pseudoviruses with diverse SARS-CoV-2 spike variants. Most participants had T helper type 1 (TH1)-skewed T cell immune responses with RBD-specific CD8+ and CD4+ T cell expansion. Interferon-γ was produced by a large fraction of RBD-specific CD8+ and CD4+ T cells. The robust RBD-specific antibody, T cell and favourable cytokine responses induced by the BNT162b1 mRNA vaccine suggest that it has the potential to protect against COVID-19 through multiple beneficial mechanisms.

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Author and article information

Journal

Journal ID (nlm-ta): Science

Journal ID (iso-abbrev): Science

Journal ID (publisher-id): SCIENCE

Title: Science (New York, N.y.)

Publisher: American Association for the Advancement of Science

ISSN (Print): 0036-8075

ISSN (Electronic): 1095-9203

Publication date (Electronic): 30 April 2021

Electronic Location Identifier: eabh1282

Affiliations

[1 ]Department of Infectious Disease, Imperial College London, London, UK.

[2 ]Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

[3 ]National Infection Service, Public Health England, Porton Down, UK.

[4 ]St Bartholomew’s Hospital, Barts Health NHS Trust, London, UK.

[5 ]Royal Free London NHS Foundation Trust, London, UK.

[6 ]Division of Medicine, University College London, London, UK.

[7 ]James Wigg Practice, Kentish Town, London, UK.

[8 ]Division of Infection and Immunity, University College London, London, UK.

[9 ]Institute of Cardiovascular Science, University College London, London, UK.

[10 ]Academic Rheumatology, Clinical Sciences, Nottingham City Hospital, Nottingham, UK.

[11 ]NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK.

[12 ]Department of Immunology and Inflammation, Imperial College London, London, UK.

[13 ]Lung Division, Royal Brompton and Harefield Hospitals, London, UK.

Author notes

[* ]Corresponding author: Email: r.boyton@ 123456imperial.ac.uk

[†]

These authors contributed equally to this work.

[§]

These authors contributed equally to this work.

[‡]

UK COVIDsortium Investigators and UK COVIDsortium Immune Correlates Network collaborators and affiliations are listed in the supplementary materials.

Author information

Catherine J. Reynolds https://orcid.org/0000-0002-1371-653X

Corinna Pade https://orcid.org/0000-0003-0626-2346

Joseph M. Gibbons https://orcid.org/0000-0002-7238-2381

David K. Butler https://orcid.org/0000-0003-1882-8159

Ashley D. Otter https://orcid.org/0000-0002-8317-9194

Katia Menacho https://orcid.org/0000-0001-5183-5655

Marianna Fontana https://orcid.org/0000-0002-9233-9831

Angelique Smit https://orcid.org/0000-0002-2144-1249

Jane E. Sackville-West https://orcid.org/0000-0001-7724-8125

Teresa Cutino-Moguel https://orcid.org/0000-0002-1726-4278

Mala K. Maini https://orcid.org/0000-0001-6384-1462

Benjamin Chain https://orcid.org/0000-0002-7417-3970

Mahdad Noursadeghi https://orcid.org/0000-0002-4774-0853

Tim Brooks https://orcid.org/0000-0002-3783-1284

Amanda Semper https://orcid.org/0000-0003-3656-1363

Charlotte Manisty https://orcid.org/0000-0003-0245-7090

Thomas A. Treibel https://orcid.org/0000-0003-1560-7414

James C. Moon https://orcid.org/0000-0001-8071-1491

Ana M. Valdes https://orcid.org/0000-0003-1141-4471

Áine McKnight https://orcid.org/0000-0002-8113-817X

Daniel M. Altmann https://orcid.org/0000-0002-2436-6192

Rosemary Boyton https://orcid.org/0000-0002-5608-0797

Article

Publisher ID: abh1282

DOI: 10.1126/science.abh1282

PMC ID: 8168614

PubMed ID: 33931567

SO-VID: c1ba78e6-a12a-42cd-a2fc-69270c7b2a7a

Copyright © Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 21 February 2021

Date accepted : 26 April 2021

Funding

Funded by: doi http://dx.doi.org/10.13039/100010269, Wellcome;

Award ID: 214191/Z/18/Z

Funded by: doi http://dx.doi.org/10.13039/100010269, Wellcome;

Award ID: 207511/Z/17/Z

Funded by: doi http://dx.doi.org/10.13039/501100000272, National Institute for Health Research;