Heterologous Gam-COVID-Vac (Sputnik V) / mRNA-1273 (Moderna) vaccination induces a stronger humoral response than homologous Sputnik V in a real-world data analysis

Abstract

Introduction: Growing data are demonstrating safety and immunogenicity of heterologous vaccination schemes against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. This strategy opens up the possibility of a shorter path towards the end of the pandemic. Objective: To compare the homologous prime-boost vaccination scheme of Gam-COVID-Vac (Sputnik V, SpV) to its heterologous combination with mRNA-1273 (Moderna, Mod) vaccine. Methods: SARS-CoV-2 anti-spike (S)-receptor binding domain (RBD) IgG concentration was assessed three to seven weeks after complete vaccination. Reactogenicity was evaluated by declared side events and medical assistance required until day 7 post-boost. Results: Of 190 participants enrolled, 105 received homologous SpV/SpV and the remaining heterologous SpV/Mod vaccination scheme, respectively. Median (interquartile range, IQR) age was 54 (37-63) years, 132 (69.5%) were female and 46 (24.2%) individuals had a prior confirmed COVID-19. Anti-S-RBD IgG median (IQR) titers were significantly higher for SpV/Mod [2511 (1476-3992) BAU/mL] than for SpV/SpV [582 (209-1609) BAU/mL, p<0.001] vaccination scheme. In a linear model adjusted for age, gender, time to the serological assay and time between doses, SpV/Mod [4.154 (6.585-615.554), p<0.001] and prior COVID [3.732 (8.641-202.010), p<0.001] were independently associated with higher anti-S-RBD IgG values. A higher frequency of mild-moderate adverse effects was associated with the heterologous scheme, although it was well tolerated by all individuals and no medical assistance was required. Conclusion: The heterologous SpV/Mod combination against SARS-CoV-2 is well tolerated and significantly increases humoral immune response as compared to the homologous SpV/SpV immunization.