Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1 nCoV-19 and BNT162b2: a prospective cohort study
Heterologous vaccine regimens have gained substantial interest as a way to mitigate intermittent supply shortages and to ameliorate the immunogenicity and safety of COVID-19 vaccines. Despite insufficient robust immunogenicity and safety data for heterologous ChAdOx1 nCov-19 and mRNA vaccination, the regimen has already commenced in several countries. David Hillus and colleagues conducted research under the title “Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunization with ChAdOx1 nCoV-19 and BNT162b2: a prospective cohort study” published in the Nature Medicine open access journal. The summary of this study is given below:
Objective:
To evaluate the immunogenicity and reactogenicity of heterologous immunizations with ChAdOx1 nCov-19 (AstraZeneca, Cambridge, UK) and BNT162b2 (Pfizer-BioNTech, Mainz, Germany) in comparison with homologous BNT162b2 and ChAdOx1 nCov-19 immunization.
Method:
This is an interim analysis of a prospective observational cohort study conducted with healthcare workers in Berlin (Germany) who were administered either heterologous ChAdOx1 nCov-19–BNT162b2 or homologous ChAdOx1 nCov-19 vaccination with an interval of 10–12-week or homologous BNT162b2 vaccination with a 3-week vaccine interval. Reactogenicity was assessed after the first and second vaccination with the help of electronic questionnaires on days 1, 3, 5, and 7. Immunogenicity was assessed by the presence of SARS-CoV-2-specific antibodies, a pseudovirus neutralization assay against two variants of concerns (alpha [B.1.1.7] and beta [B.1.351]), by an RBD–ACE2 binding inhibition assay, and anti-S1-IgG avidity. The T-cell reactivity was assessed by the IFN-γ release assay.
Findings:
The study reports that all three regimens were well tolerated and there were no major differences in reactogenicity between the prime-boost regimens. Local reactions were commonly observed for all vaccines. Additionally, systemic reactions, including severe reactions, were recurring after prime immunisation with ChAdOx1 nCov-19, whereas reactogenicity of homologous BNT162b2, homologous ChAdOx1 nCoV19, and heterologous ChAdOx1 nCoV19–BNT162b2 were not different, with slightly low systemic reactions after heterologous ChAdOx1 nCov-19–BNT162b2 and homologous ChAdOx1 nCov-19.
It was found that S1-reactive T-cells, anti-S1-IgG avidity, and neutralizing capacity against two variants of concern were significantly elevated 3 weeks after heterologous ChAdOx1 nCov-19– BNT162b2 boost as compared with homologous BNT162b2 and ChAdOx1 nCov-19 boost vaccination.
There was no significant difference observed in anti-RBD-IgG levels, anti-S1-IgG levels, and neutralization capacity as evaluated by sVNT. Additionally, an increase in anti-S1-IgG avidity 3 weeks was observed after heterologous ChAdOx1 nCov-19–BNT162b2 boost compared with homologous BNT162b2 boost.
Lastly, while all three vaccine regimens prompt robust T-cell responses, the T-cell reactivity was significantly increased after heterologous immunization.
Limitation:
The study was not masked and didn’t include a placebo group. Secondly, due to the low sample size, the adverse events were not addressed efficiently. The study doesn’t include the randomized allocation of different vaccination regimens. It is unclear whether increased immunogenicity of heterologous vaccination helps to improve protection.
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