Abstract
Following severe adverse reactions to the AstraZeneca ChAdOx1-S-nCoV-19 vaccine1,2, European health authorities recommended that patients under the age of 55 years who received one dose of ChAdOx1-S-nCoV-19 receive a second dose of the Pfizer BNT162b2 vaccine as a booster. However, the effectiveness and the immunogenicity of this vaccination regimen have not been formally tested. Here we show that the heterologous ChAdOx1-S-nCoV-19 and BNT162b2 combination confers better protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than the homologous BNT162b2 and BNT162b2 combination in a real-world observational study of healthcare workers (n = 13,121). To understand the underlying mechanism, we conducted a longitudinal survey of the anti-spike immunity conferred by each vaccine combination. Both combinations induced strong anti-spike antibody responses, but sera from heterologous vaccinated individuals displayed a stronger neutralizing activity regardless of the SARS-CoV-2 variant. This enhanced neutralizing potential correlated with increased frequencies of switched and activated memory B cells that recognize the SARS-CoV-2 receptor binding domain. The ChAdOx1-S-nCoV-19 vaccine induced a weaker IgG response but a stronger T cell response than the BNT162b2 vaccine after the priming dose, which could explain the complementarity of both vaccines when used in combination. The heterologous vaccination regimen could therefore be particularly suitable for immunocompromised individuals.
Highlights
Heterologous prime/boost vaccinations have been reported to be more immunogenic than homologous ones in experimental settings[11]
We report that the heterologous ChAd/BNT vaccination confers better protection against infection, which is associated with more switched memory B cell (mBC) and higher virus neutralizing Ab titres, irrespective of the variant analysed
This finding is of particular importance considering the global rise of the SARS-CoV-2 delta variant[15]
Summary
Heterologous prime/boost vaccinations have been reported to be more immunogenic than homologous ones in experimental settings[11]. R. et al Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity. Barros-Martins, J. et al Immune responses against SARS-CoV-2 variants after heterologous and homologous ChAdOx1 nCoV-19/BNT162b2 vaccination. (D-F) Sera from ChAd/BNT (n=29) or BNT/BNT (n=31) individuals were assayed in triplicate for their capacity to neutralize the entry of virus-like particles pseudotyped with Wuhan-strain SARS-CoV-2 envelope (D) or in duplicate for their capacity to neutralize the infection of Vero E6 cells by neutralization, relative to a positive control (D) or the PRNT50 (E), and are expressed as dot plots, one dot corresponding to one patient. IFNγ was measured by Elisa in the supernatant. (G-H) Flow cytometry shown for the indicated comparisons, when significant, or nearly significant
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
