Induction of Fc-dependent Functional Antibodies Against Different Variants of SARS-CoV-2 Varies by Vaccine Type and Prior Infection

Overview

Journal Commun Med (Lond)

Publisher Nature Portfolio

Specialty General Medicine

Date 2024 Dec 20

PMID 39702507

Authors

Alexander W Harris

Liriye Kurtovic

Jeane Nogueira

Isabel Bouzas

D Herbert Opi

Bruce D Wines

Wen Shi Lee

P Mark Hogarth

Pantelis Poumbourios

Heidi E Drummer

Clarissa Valim

Luis Cristovao Porto

James G Beeson

Affiliations

Soon will be listed here.

Abstract

Background: SARS-CoV-2 transmission and COVID-19 disease severity is influenced by immunity from natural infection and/or vaccination. Population-level immunity is complicated by the emergence of viral variants. Antibody Fc-dependent effector functions are as important mediators in immunity. However, their induction in populations with diverse infection and/or vaccination histories and against variants remains poorly defined.

Methods: We evaluated Fc-dependent functional antibodies following vaccination with two widely used vaccines, AstraZeneca (AZ) and Sinovac (SV), including antibody binding of Fcγ-receptors and complement-fixation in vaccinated Brazilian adults (n = 222), some of who were previously infected with SARS-CoV-2, as well as adults with natural infection only (n = 200). IgG, IgM, IgA, and IgG subclasses were also quantified.

Results: AZ induces greater Fcγ-receptor-binding (types I, IIa, and IIIa/b) antibodies than SV or natural infection. Previously infected individuals have significantly greater vaccine-induced responses compared to naïve counterparts. Fcγ-receptor-binding is highest among AZ vaccinated individuals with a prior infection, for all receptor types, and substantial complement-fixing activity is only seen among this group. SV induces higher IgM than AZ, but this does not drive better complement-fixing activity. Some SV responses are associated with subject age, whereas AZ responses are not. Importantly, functional antibody responses are well retained against the Omicron BA.1 S protein, being best retained for Fcγ-receptor-1 binding, and are higher for AZ than SV.

Conclusions: Hybrid immunity, from combined natural exposure and vaccination, generates strong Fc-mediated antibody functions which may contribute to immunity against evolving SARS-CoV-2 variants. Understanding determinants of Fc-mediated functions may enable future vaccines with greater efficacy against different variants.

References

Fowkes F, McGready R, Cross N, Hommel M, Simpson J, Elliott S . New insights into acquisition, boosting, and longevity of immunity to malaria in pregnant women. J Infect Dis. 2012; 206(10):1612-21. PMC: 3475637. DOI: 10.1093/infdis/jis566. View

Mok C, Cohen C, Cheng S, Chen C, Kwok K, Yiu K . Comparison of the immunogenicity of BNT162b2 and CoronaVac COVID-19 vaccines in Hong Kong. Respirology. 2021; 27(4):301-310. PMC: 8934254. DOI: 10.1111/resp.14191. View

Kurtovic L, Boyle M, Opi D, Kennedy A, Tham W, Reiling L . Complement in malaria immunity and vaccines. Immunol Rev. 2019; 293(1):38-56. PMC: 6972673. DOI: 10.1111/imr.12802. View

Xu Q, Xie L, Zheng X, Liang X, Jia Z, Liu Y . Anti-SARS-CoV-2 IgM Secondary Response Was Suppressed by Preexisting Immunity in Vaccinees: A Prospective, Longitudinal Cohort Study over 456 Days. Vaccines (Basel). 2023; 11(1). PMC: 9862995. DOI: 10.3390/vaccines11010188. View

Lu L, Chen L, Zhang R, Tsang O, Chan J, Tam A . Boosting of serum neutralizing activity against the Omicron variant among recovered COVID-19 patients by BNT162b2 and CoronaVac vaccines. EBioMedicine. 2022; 79:103986. PMC: 8989491. DOI: 10.1016/j.ebiom.2022.103986. View

Yaffe Z, Naiman N, Slyker J, Wines B, Richardson B, Hogarth P . Improved HIV-positive infant survival is correlated with high levels of HIV-specific ADCC activity in multiple cohorts. Cell Rep Med. 2021; 2(4):100254. PMC: 8080236. DOI: 10.1016/j.xcrm.2021.100254. View

Verderese J, Stepanova M, Lam B, Racila A, Kolacevski A, Allen D . Neutralizing Monoclonal Antibody Treatment Reduces Hospitalization for Mild and Moderate Coronavirus Disease 2019 (COVID-19): A Real-World Experience. Clin Infect Dis. 2021; 74(6):1063-1069. PMC: 8344419. DOI: 10.1093/cid/ciab579. View

Alter G, Yu J, Liu J, Chandrashekar A, Borducchi E, Tostanoski L . Immunogenicity of Ad26.COV2.S vaccine against SARS-CoV-2 variants in humans. Nature. 2021; 596(7871):268-272. PMC: 8357629. DOI: 10.1038/s41586-021-03681-2. View

Mackin S, Desai P, Whitener B, Karl C, Liu M, Baric R . Fc-γR-dependent antibody effector functions are required for vaccine-mediated protection against antigen-shifted variants of SARS-CoV-2. Nat Microbiol. 2023; 8(4):569-580. PMC: 10797606. DOI: 10.1038/s41564-023-01359-1. View

10.

Tay M, Wiehe K, Pollara J . Antibody-Dependent Cellular Phagocytosis in Antiviral Immune Responses. Front Immunol. 2019; 10:332. PMC: 6404786. DOI: 10.3389/fimmu.2019.00332. View

11.

Kurtovic L, Agius P, Feng G, Drew D, Ubillos I, Sacarlal J . Induction and decay of functional complement-fixing antibodies by the RTS,S malaria vaccine in children, and a negative impact of malaria exposure. BMC Med. 2019; 17(1):45. PMC: 6388494. DOI: 10.1186/s12916-019-1277-x. View

12.

Bournazos S, Klein F, Pietzsch J, Seaman M, Nussenzweig M, Ravetch J . Broadly neutralizing anti-HIV-1 antibodies require Fc effector functions for in vivo activity. Cell. 2014; 158(6):1243-1253. PMC: 4167398. DOI: 10.1016/j.cell.2014.08.023. View

13.

Feng G, Wines B, Kurtovic L, Chan J, Boeuf P, Mollard V . Mechanisms and targets of Fcγ-receptor mediated immunity to malaria sporozoites. Nat Commun. 2021; 12(1):1742. PMC: 7979888. DOI: 10.1038/s41467-021-21998-4. View

14.

Robertson L, Price R, Moore J, Curry G, Farnan J, Black A . IgG antibody production and persistence to 6 months following SARS-CoV-2 vaccination: A Northern Ireland observational study. Vaccine. 2022; 40(18):2535-2539. PMC: 8900637. DOI: 10.1016/j.vaccine.2022.02.087. View

15.

Ewer K, Barrett J, Belij-Rammerstorfer S, Sharpe H, Makinson R, Morter R . T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial. Nat Med. 2020; 27(2):270-278. DOI: 10.1038/s41591-020-01194-5. View

16.

Chan C, Seah S, Chye D, Massey S, Torres M, Lim A . The Fc-mediated effector functions of a potent SARS-CoV-2 neutralizing antibody, SC31, isolated from an early convalescent COVID-19 patient, are essential for the optimal therapeutic efficacy of the antibody. PLoS One. 2021; 16(6):e0253487. PMC: 8221499. DOI: 10.1371/journal.pone.0253487. View

17.

Ruggiero A, Piubelli C, Calciano L, Accordini S, Valenti M, Dalle Carbonare L . SARS-CoV-2 vaccination elicits unconventional IgM specific responses in naïve and previously COVID-19-infected individuals. EBioMedicine. 2022; 77:103888. PMC: 8858081. DOI: 10.1016/j.ebiom.2022.103888. View

18.

Cyprian F, Suleman M, Abdelhafez I, Doudin A, Masud Danjuma I, Mir F . Complement C5a and Clinical Markers as Predictors of COVID-19 Disease Severity and Mortality in a Multi-Ethnic Population. Front Immunol. 2021; 12:707159. PMC: 8710484. DOI: 10.3389/fimmu.2021.707159. View

19.

Kaplonek P, Cizmeci D, Kwatra G, Izu A, Shih-Lu Lee J, Bertera H . ChAdOx1 nCoV-19 (AZD1222) vaccine-induced Fc receptor binding tracks with differential susceptibility to COVID-19. Nat Immunol. 2023; 24(7):1161-1172. PMC: 10307634. DOI: 10.1038/s41590-023-01513-1. View

20.

Stowe J, Andrews N, Kirsebom F, Ramsay M, Lopez Bernal J . Effectiveness of COVID-19 vaccines against Omicron and Delta hospitalisation, a test negative case-control study. Nat Commun. 2022; 13(1):5736. PMC: 9523190. DOI: 10.1038/s41467-022-33378-7. View