The Magnitude and Timing of Recalled Immunity After Breakthrough Infection is Shaped by SARS-CoV-2 Variants

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2022 Jun 11

PMID 35690062

Authors

Marios Koutsakos

Wen Shi Lee

Arnold Reynaldi

Hyon-Xhi Tan

Grace Gare

Paul Kinsella

Kwee Chin Liew

George Taiaroa

Deborah A Williamson

Helen E Kent

Eva Stadler

Deborah Cromer

David S Khoury

Adam K Wheatley

Jennifer A Juno

Miles P Davenport

Stephen J Kent

Affiliations

Soon will be listed here.

Abstract

Vaccination against SARS-CoV-2 protects from infection and improves clinical outcomes in breakthrough infections, likely reflecting residual vaccine-elicited immunity and recall of immunological memory. Here, we define the early kinetics of spike-specific humoral and cellular immunity after vaccination of seropositive individuals and after Delta or Omicron breakthrough infection in vaccinated individuals. Early longitudinal sampling revealed the timing and magnitude of recall, with the phenotypic activation of B cells preceding an increase in neutralizing antibody titers. While vaccination of seropositive individuals resulted in robust recall of humoral and T cell immunity, recall of vaccine-elicited responses was delayed and variable in magnitude during breakthrough infections and depended on the infecting variant of concern. While the delayed kinetics of immune recall provides a potential mechanism for the lack of early control of viral replication, the recall of antibodies coincided with viral clearance and likely underpins the protective effects of vaccination against severe COVID-19.

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References

Ferdinands J, Thompson M, Blanton L, Spencer S, Grant L, Fry A . Does influenza vaccination attenuate the severity of breakthrough infections? A narrative review and recommendations for further research. Vaccine. 2021; 39(28):3678-3695. DOI: 10.1016/j.vaccine.2021.05.011. View

Backer J, Eggink D, Andeweg S, Veldhuijzen I, van Maarseveen N, Vermaas K . Shorter serial intervals in SARS-CoV-2 cases with Omicron BA.1 variant compared with Delta variant, the Netherlands, 13 to 26 December 2021. Euro Surveill. 2022; 27(6). PMC: 8832521. DOI: 10.2807/1560-7917.ES.2022.27.6.2200042. View

Corman V, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu D . Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill. 2020; 25(3). PMC: 6988269. DOI: 10.2807/1560-7917.ES.2020.25.3.2000045. View

Tenforde M, Self W, Adams K, Gaglani M, Ginde A, McNeal T . Association Between mRNA Vaccination and COVID-19 Hospitalization and Disease Severity. JAMA. 2021; 326(20):2043-2054. PMC: 8569602. DOI: 10.1001/jama.2021.19499. View

Weinreich D, Sivapalasingam S, Norton T, Ali S, Gao H, Bhore R . REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19. N Engl J Med. 2020; 384(3):238-251. PMC: 7781102. DOI: 10.1056/NEJMoa2035002. View

Khoury D, Cromer D, Reynaldi A, Schlub T, Wheatley A, Juno J . Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med. 2021; 27(7):1205-1211. DOI: 10.1038/s41591-021-01377-8. View

Kissler S, Fauver J, Mack C, Tai C, Breban M, Watkins A . Viral Dynamics of SARS-CoV-2 Variants in Vaccinated and Unvaccinated Persons. N Engl J Med. 2021; 385(26):2489-2491. PMC: 8693673. DOI: 10.1056/NEJMc2102507. View

Nyberg T, Ferguson N, Nash S, Webster H, Flaxman S, Andrews N . Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study. Lancet. 2022; 399(10332):1303-1312. PMC: 8926413. DOI: 10.1016/S0140-6736(22)00462-7. View

Wheatley A, Juno J, Wang J, Selva K, Reynaldi A, Tan H . Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19. Nat Commun. 2021; 12(1):1162. PMC: 7896046. DOI: 10.1038/s41467-021-21444-5. View

10.

Tang P, Hasan M, Chemaitelly H, Yassine H, Benslimane F, Al Khatib H . BNT162b2 and mRNA-1273 COVID-19 vaccine effectiveness against the SARS-CoV-2 Delta variant in Qatar. Nat Med. 2021; 27(12):2136-2143. DOI: 10.1038/s41591-021-01583-4. View

11.

Sahin U, Muik A, Vogler I, Derhovanessian E, Kranz L, Vormehr M . BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans. Nature. 2021; 595(7868):572-577. DOI: 10.1038/s41586-021-03653-6. View

12.

Wragg K, Lee W, Koutsakos M, Tan H, Amarasena T, Reynaldi A . Establishment and recall of SARS-CoV-2 spike epitope-specific CD4 T cell memory. Nat Immunol. 2022; 23(5):768-780. DOI: 10.1038/s41590-022-01175-5. View

13.

Juno J, Tan H, Lee W, Reynaldi A, Kelly H, Wragg K . Humoral and circulating follicular helper T cell responses in recovered patients with COVID-19. Nat Med. 2020; 26(9):1428-1434. DOI: 10.1038/s41591-020-0995-0. View

14.

Cameroni E, Bowen J, Rosen L, Saliba C, Zepeda S, Culap K . Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift. Nature. 2022; 602(7898):664-670. PMC: 9531318. DOI: 10.1038/s41586-021-04386-2. View

15.

Singanayagam A, Hakki S, Dunning J, Madon K, Crone M, Koycheva A . Community transmission and viral load kinetics of the SARS-CoV-2 delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: a prospective, longitudinal, cohort study. Lancet Infect Dis. 2021; 22(2):183-195. PMC: 8554486. DOI: 10.1016/S1473-3099(21)00648-4. View

16.

Chen P, Nirula A, Heller B, Gottlieb R, Boscia J, Morris J . SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19. N Engl J Med. 2020; 384(3):229-237. PMC: 7646625. DOI: 10.1056/NEJMoa2029849. View

17.

Gagne M, Corbett K, Flynn B, Foulds K, Wagner D, Andrew S . Protection from SARS-CoV-2 Delta one year after mRNA-1273 vaccination in rhesus macaques coincides with anamnestic antibody response in the lung. Cell. 2021; 185(1):113-130.e15. PMC: 8639396. DOI: 10.1016/j.cell.2021.12.002. View

18.

Carreno J, Alshammary H, Tcheou J, Singh G, Raskin A, Kawabata H . Activity of convalescent and vaccine serum against SARS-CoV-2 Omicron. Nature. 2022; 602(7898):682-688. DOI: 10.1038/s41586-022-04399-5. View

19.

Patel M, York I, Monto A, Thompson M, Fry A . Immune-mediated attenuation of influenza illness after infection: opportunities and challenges. Lancet Microbe. 2022; 2(12):e715-e725. DOI: 10.1016/S2666-5247(21)00180-4. View

20.

. Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial. Lancet. 2021; 397(10289):2049-2059. PMC: 8121538. DOI: 10.1016/S0140-6736(21)00897-7. View