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ChAdOx1 nCoV-19 (AZD1222) vaccine-induced Fc receptor binding tracks with differential susceptibility to COVID-19.

ABSTRACT: Despite the success of COVID-19 vaccines, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern have emerged that can cause breakthrough infections. Although protection against severe disease has been largely preserved, the immunological mediators of protection in humans remain undefined. We performed a substudy on the ChAdOx1 nCoV-19 (AZD1222) vaccinees enrolled in a South African clinical trial. At peak immunogenicity, before infection, no differences were observed in immunoglobulin (Ig)G1-binding antibody titers; however, the vaccine induced different Fc-receptor-binding antibodies across groups. Vaccinees who resisted COVID-19 exclusively mounted FcγR3B-binding antibodies. In contrast, enhanced IgA and IgG3, linked to enriched FcγR2B binding, was observed in individuals who experienced breakthrough. Antibodies unable to bind to FcγR3B led to immune complex clearance and resulted in inflammatory cascades. Differential antibody binding to FcγR3B was linked to Fc-glycosylation differences in SARS-CoV-2-specific antibodies. These data potentially point to specific FcγR3B-mediated antibody functional profiles as critical markers of immunity against COVID-19.

SUBMITTER: Kaplonek P

PROVIDER: S-EPMC10307634 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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ChAdOx1 nCoV-19 (AZD1222) vaccine-induced Fc receptor binding tracks with differential susceptibility to COVID-19.

Kaplonek Paulina P Cizmeci Deniz D Kwatra Gaurav G Izu Alane A Lee Jessica Shih-Lu JS Bertera Harry L HL Fischinger Stephanie S Mann Colin C Amanat Fatima F Wang Wenjun W Koen Anthonet L AL Fairlie Lee L Cutland Clare L CL Ahmed Khatija K Dheda Keertan K Barnabas Shaun L SL Bhorat Qasim Ebrahim QE Briner Carmen C Krammer Florian F Saphire Erica Ollman EO Gilbert Sarah C SC Lambe Teresa T Pollard Andrew J AJ Nunes Marta M Wuhrer Manfred M Lauffenburger Douglas A DA Madhi Shabir A SA Alter Galit G

Nature immunology 20230615 7

Despite the success of COVID-19 vaccines, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern have emerged that can cause breakthrough infections. Although protection against severe disease has been largely preserved, the immunological mediators of protection in humans remain undefined. We performed a substudy on the ChAdOx1 nCoV-19 (AZD1222) vaccinees enrolled in a South African clinical trial. At peak immunogenicity, before infection, no differences were observed i ...[more]

PMID: 37322179

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Project description:BackgroundThe safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known.MethodsIn this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru.ResultsA total of 32,451 participants underwent randomization, in a 2:1 ratio, to receive AZD1222 (21,635 participants) or placebo (10,816 participants). AZD1222 was safe, with low incidences of serious and medically attended adverse events and adverse events of special interest; the incidences were similar to those observed in the placebo group. Solicited local and systemic reactions were generally mild or moderate in both groups. Overall estimated vaccine efficacy was 74.0% (95% confidence interval [CI], 65.3 to 80.5; P<0.001) and estimated vaccine efficacy was 83.5% (95% CI, 54.2 to 94.1) in participants 65 years of age or older. High vaccine efficacy was consistent across a range of demographic subgroups. In the fully vaccinated analysis subgroup, no severe or critical symptomatic Covid-19 cases were observed among the 17,662 participants in the AZD1222 group; 8 cases were noted among the 8550 participants in the placebo group (<0.1%). The estimated vaccine efficacy for preventing SARS-CoV-2 infection (nucleocapsid antibody seroconversion) was 64.3% (95% CI, 56.1 to 71.0; P<0.001). SARS-CoV-2 spike protein binding and neutralizing antibodies increased after the first dose and increased further when measured 28 days after the second dose.ConclusionsAZD1222 was safe and efficacious in preventing symptomatic and severe Covid-19 across diverse populations that included older adults. (Funded by AstraZeneca and others; ClinicalTrials.gov number, NCT04516746.).

Project description:BackgroundThere are known differences in vaccine reactogenicity and immunogenicity by sex. Females have been shown to report greater reactogenicity and generate higher humoral and cellular immune responses than males following vaccination with several different vaccines. Whether this is also the case for COVID-19 vaccines is currently unknown, as COVID-19 vaccine study data disaggregated by sex are not routinely reported. Therefore, we have assessed the influence of sex on reactogenicity, immunogenicity and efficacy of COVID-19 vaccine ChAdOx1 nCoV-19.MethodsVaccine efficacy was assessed in 15169 volunteers enrolled into single-blind randomised controlled trials of ChAdOx1 nCoV-19 in Brazil and the UK, with the primary endpoint defined as nucleic acid amplification test (NAAT)-positive symptomatic SARS-CoV-2 infection. All participants were electronically randomised to receive two standard doses of vaccine or the control product. Logistic regression models were fitted to explore the effect of age and sex on reactogenicity, and linear models fitted to log-transformed values for immunogenicity data. Reactogenicity data were taken from self-reported diaries of 788 trial participants. Pseudovirus neutralisation assay data were available from 748 participants and anti-SARS-CoV-2 spike IgG assay data from 1543 participants.Findings7619 participants received ChAdOx1 nCoV-19 and 7550 received the control. Vaccine efficacy in participants after two doses of ChAdOx1 nCoV-19 (4243 females and 3376 males) was 66.1% (95% CI 55.9-73.9%) in males and 59.9% (95% CI 49.8-67.9%) in females; with no evidence of a difference in efficacy between the sexes (vaccine by sex interaction term P=0.3359). A small, statistically significant difference in anti-spike IgG was observed (adjusted GMR 1.14; 95% CI 1.04-1.26), with higher titres in females than males, but there were no statistically significant differences in other immunological endpoints. Whilst the majority of individuals reported at least one systemic reaction following a first dose of ChAdOx1 nCoV-19, females were twice as likely as males to report any systemic reaction after a first dose (OR 1.95; 95% CI 1.37-2.77). Measured fever of 38°C or above was reported in 5% of females and 1% of males following first doses. Headache and fatigue were the most commonly reported reactions in both sexes.InterpretationOur results show that there is no evidence of difference in efficacy of the COVID-19 vaccine ChAdOx1 nCoV-19 in males and females. Greater reactogenicity in females was not associated with any difference in vaccine efficacy.FundingStudies were registered with ISRCTN 90906759 (COV002) and ISRCTN 89951424 (COV003) and follow-up is ongoing. Funding was received from the UK Research and Innovation, Engineering and Physical Sciences Research Council, National Institute for Health Research, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research Oxford Biomedical Research Centre, Chinese Academy of Medical Sciences Innovation Fund for Medical Science, Thames Valley and South Midlands NIHR Clinical Research Network, the Lemann Foundation, Rede D'Or, the Brava and Telles Foundation, the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazil, and AstraZeneca.

Dataset Information

ChAdOx1 nCoV-19 (AZD1222) vaccine-induced Fc receptor binding tracks with differential susceptibility to COVID-19.

Publications

ChAdOx1 nCoV-19 (AZD1222) vaccine-induced Fc receptor binding tracks with differential susceptibility to COVID-19.

Similar Datasets

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