A third vaccine dose equalizes the levels of effectiveness and immunogenicity of heterologous or homologous COVID-19 vaccine regimens

BackgroungTo cope with the persistence of the Covid-19 epidemic and the decrease in antibody levels following vaccination, a third dose of vaccine has been recommended in the general population. However, several vaccine regimens had been used initially, and the heterologous ChadOx1-S/BNT162b2 regimen had shown better efficacy and immunogenicity than the homologous BNT162b2/BNT162b2 regimen. AimWe wanted to determine if this benefit was retained after the third dose. MethodsWe combined an observational study of SARS-COV-2 infections among vaccinated healthcare workers at the University-Hospital of Lyon, France, with an analysis of immunological parameters before and after the third mRNA vaccine dose. ResultsFollowing the second vaccine dose, heterologous vaccination regimens were more protective against infection than homologous regimens, but this was no longer the case after the third dose. RBD-specific IgG levels and serum neutralization capacity against different SARS-CoV-2 variants were higher after the third dose than after the second dose in the homologous regimen group, but not in the heterologous group. ConclusionThe advantage conferred by heterologous vaccination is lost after the third dose both in terms of protection and immunogenicity. Immunological measurements suggest that heterologous vaccination induces maximal immunity after the second dose, whereas the third dose is required to reach the same level in individuals with a homologous regimen.