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Immunogenicity and reactogenicity of heterologous ChAdOx1 nCoV-19/mRNA vaccination.

ABSTRACT: Heterologous priming with the ChAdOx1 nCoV-19 vector vaccine followed by boosting with a messenger RNA vaccine (BNT162b2 or mRNA-1273) is currently recommended in Germany, although data on immunogenicity and reactogenicity are not available. In this observational study we show that, in healthy adult individuals (n = 96), the heterologous vaccine regimen induced spike-specific IgG, neutralizing antibodies and spike-specific CD4 T cells, the levels of which which were significantly higher than after homologous vector vaccine boost (n = 55) and higher or comparable in magnitude to homologous mRNA vaccine regimens (n = 62). Moreover, spike-specific CD8 T cell levels after heterologous vaccination were significantly higher than after both homologous regimens. Spike-specific T cells were predominantly polyfunctional with largely overlapping cytokine-producing phenotypes in all three regimens. Recipients of both the homologous vector regimen and the heterologous vector/mRNA combination reported greater reactogenicity following the priming vector vaccination, whereas heterologous boosting was well tolerated and comparable to homologous mRNA boosting. Taken together, heterologous vector/mRNA boosting induces strong humoral and cellular immune responses with acceptable reactogenicity profiles.

SUBMITTER: Schmidt T

PROVIDER: S-EPMC8440177 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundHeterologous vaccine regimens have been widely discussed as a way to mitigate intermittent supply shortages and to improve immunogenicity and safety of COVID-19 vaccines. We aimed to assess the reactogenicity and immunogenicity of heterologous immunisations with ChAdOx1 nCov-19 (AstraZeneca, Cambridge, UK) and BNT162b2 (Pfizer-BioNtech, Mainz, Germany) compared with homologous BNT162b2 and ChAdOx1 nCov-19 immunisation.MethodsThis is an interim analysis of a prospective observational cohort study enrolling health-care workers in Berlin (Germany) who received either homologous ChAdOx1 nCov-19 or heterologous ChAdOx1 nCov-19-BNT162b2 vaccination with a 10-12-week vaccine interval or homologous BNT162b2 vaccination with a 3-week vaccine interval. We assessed reactogenicity after the first and second vaccination by use of electronic questionnaires on days 1, 3, 5, and 7. Immunogenicity was measured by the presence of SARS-CoV-2-specific antibodies (full spike-IgG, S1-IgG, and RBD-IgG), by an RBD-ACE2 binding inhibition assay (surrogate SARS-CoV-2 virus neutralisation test), a pseudovirus neutralisation assay against two variants of concerns (alpha [B.1.1.7] and beta [B.1.351]), and anti-S1-IgG avidity. T-cell reactivity was measured by IFN-γ release assay.FindingsBetween Dec 27, 2020, and June 14, 2021, 380 participants were enrolled in the study, with 174 receiving homologous BNT162b2 vaccination, 38 receiving homologous ChAdOx1 nCov-19 vaccination, and 104 receiving ChAdOx1 nCov-19-BNT162b2 vaccination. Systemic symptoms were reported by 103 (65%, 95% CI 57·1-71·8) of 159 recipients of homologous BNT162b2, 14 (39%, 24·8-55·1) of 36 recipients of homologous ChAdOx1 nCov-19, and 51 (49%, 39·6-58·5) of 104 recipients of ChAdOx1 nCov-19-BNT162b2 after the booster immunisation. Median anti-RBD IgG levels 3 weeks after boost immunisation were 5·4 signal to cutoff ratio (S/co; IQR 4·8-5·9) in recipients of homologous BNT162b2, 4·9 S/co (4·3-5·6) in recipients of homologous ChAdOx1 nCov-19, and 5·6 S/co (5·1-6·1) in recipients of ChAdOx1 nCov-19- BNT162b2. Geometric mean of 50% inhibitory dose against alpha and beta variants were highest in recipients of ChAdOx1 nCov-19-BNT162b2 (956·6, 95% CI 835·6-1095, against alpha and 417·1, 349·3-498·2, against beta) compared with those in recipients of homologous ChAdOx1 nCov-19 (212·5, 131·2-344·4, against alpha and 48·5, 28·4-82·8, against beta; both p<0·0001) or homologous BNT162b2 (369·2, 310·7-438·6, against alpha and 72·4, 60·5-86·5, against beta; both p<0·0001). SARS-CoV-2 S1 T-cell reactivity 3 weeks after boost immunisation was highest in recipients of ChAdOx1 nCov-19-BNT162b2 (median IFN-γ concentration 4762 mIU/mL, IQR 2723-8403) compared with that in recipients of homologous ChAdOx1 nCov-19 (1061 mIU/mL, 599-2274, p<0·0001) and homologous BNT162b2 (2026 mIU/mL, 1459-4621, p=0·0008) vaccination.InterpretationThe heterologous ChAdOx1 nCov-19-BNT162b2 immunisation with 10-12-week interval, recommended in Germany, is well tolerated and improves immunogenicity compared with homologous ChAdOx1 nCov-19 vaccination with 10-12-week interval and BNT162b2 vaccination with 3-week interval. Heterologous prime-boost immunisation strategies for COVID-19 might be generally applicable.FundingForschungsnetzwerk der Universitätsmedizin zu COVID-19, the German Ministry of Education and Research, Zalando SE.

Project description:BackgroundThe effectiveness of heterologous prime-boost Coronavirus disease 2019 (Covid-19) vaccination is currently unknown.MethodsFrom individuals vaccinated with two doses against Covid-19 in Sweden until July 5, 2021 (N=3,445,061), we formed a study cohort including 94,569 individuals that had received heterologous ChAdOx1 nCoV-19 / BNT162b2 prime-boost vaccination, 16,402 individuals that received heterologous ChAdOx1 nCoV-19 / mRNA-1273 prime-boost vaccination, and 430,100 individuals that received homologous ChAdOx1 nCoV-19 / ChAdOx1 nCoV-19 prime-boost vaccination. In addition, 180,716 individuals were selected who were unvaccinated at the date of vaccination in the corresponding case. Unvaccinated individuals were censored at first dose of any vaccine. Baseline was the date of the second dose of any vaccine, with the same date in the corresponding unvaccinated individual. The outcome included incident symptomatic Covid-19 infection occurring >14 days after baseline.FindingsDuring a mean follow-up time of 76 (range 1-183) days, symptomatic Covid-19 infection was confirmed in 187 individuals with heterologous vaccine schedules (incidence rate: 2.0/100,000 person-days) and in 306 individuals from the unvaccinated control group (incidence rate: 7.1/100,000 person-days). The adjusted vaccine effectiveness was 67% (95% CI, 59-73, P<0.001) for heterologous ChAdOx1 nCoV-19 / BNT162b2 prime-boost vaccination, and 79% (95% CI, 62-88, P<0.001) for heterologous ChAdOx1 nCoV-19 / mRNA-1273 prime-boost vaccination. When combined and analysed together, the two heterologous vaccine schedules had an effectiveness of 68% (95% CI, 61-74, P<0.001) which was significantly greater (Pinteraction<0.001) than the 50% effectiveness for homologous ChAdOx1 nCoV-19 / ChAdOx1 nCoV-19 (95% CI, 41-58, P<0.001).InterpretationThe findings of this study suggest that the use of heterologous ChAdOx1 nCoV-19 and mRNA prime-boost vaccination is an effective alternative to increase population immunity against Covid-19, including against the Delta variant which dominated the confirmed cases during the study period. These findings could have important implications for vaccination strategies and logistics, and consequently in the battle against the Covid-19 pandemic.

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Immunogenicity and reactogenicity of heterologous ChAdOx1 nCoV-19/mRNA vaccination.

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