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Observational Study
. 2023 Apr;28(15):2200746.
doi: 10.2807/1560-7917.ES.2023.28.15.2200746.

A third vaccine dose equalises the levels of effectiveness and immunogenicity of heterologous or homologous COVID-19 vaccine regimens, Lyon, France, December 2021 to March 2022

Nicolas Guibert  1 , Kylian Trepat  2   3 , Bruno Pozzetto  2   4 , Laurence Josset  2   5   6 , Jean-Baptiste Fassier  1 , Omran Allatif  2 , Kahina Saker  3 , Karen Brengel-Pesce  3 , Thierry Walzer  2   7 , Philippe Vanhems  2   8   7 , Sophie Trouillet-Assant  2   3   7 ; Lyon-COVID study group  9
Affiliations
Observational Study

A third vaccine dose equalises the levels of effectiveness and immunogenicity of heterologous or homologous COVID-19 vaccine regimens, Lyon, France, December 2021 to March 2022

Nicolas Guibert et al. Euro Surveill. 2023 Apr.

Abstract

BackgroundTo 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 for the primary vaccination course, and the heterologous Vaxzevria/Comirnaty regimen had shown better efficacy and immunogenicity than the homologous Comirnaty/Comirnaty regimen.AimWe wanted to determine if this benefit was retained after a third dose of an mRNA vaccine.MethodsWe combined an observational epidemiological study of SARS-CoV-2 infections among vaccinated healthcare workers at the University Hospital of Lyon, France, with a prospective cohort study to analyse 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 (adjusted hazard ratio (HR) = 1.88; 95% confidence interval (CI): 1.18-3.00; p = 0.008), but this was no longer the case after the third dose (adjusted HR = 0.86; 95% CI: 0.72-1.02; p = 0.082). Receptor-binding domain-specific IgG levels and serum neutralisation 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 was lost after the third dose in terms of both protection and immunogenicity. Immunological measurements 1 month after vaccination 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.

Keywords: SARS-CoV-2; breakthrough infection; healthcare workers; heterologous vaccine regimens; neutralisation; vaccination.

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Conflict of interest statement

Conflict of interest: K.B.-P. is a bioMérieux employee.

Figures

Figure 1
Figure 1
Selection of healthcare workers for the epidemiological study on COVID-19 booster vaccinations, Lyon, France, 15 December 2021–21 March 2022 (n = 13,489)
Figure 2
Figure 2
Effectiveness of heterologous vs homologous COVID-19 vaccination after the third vaccine dose, healthcare workers, Lyon, France, 15 December 2021–21 March 2022 (n = 13,489)
Figure 3
Figure 3
Design of the Covid-Ser study, France January 2021–February 2022 (n = 88)
Figure 4
Figure 4
The booster dose equalises the levels of immunogenicity of heterologous or homologous vaccine regimens, France, January 2021–February 2022 (n = 88)
See this image and copyright information in PMC

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