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

OBJECTIVES: 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 out of 190 (69.5%) were female, and 46 out of 190 (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) binding antibody units (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 and moderate adverse effects was associated with the heterologous scheme (20 of 85 (23.5%) vs. 13 of 105 (12.4%); p = 0.043 and 27 of 85 (31.8%) vs. 14 of 105 (13.3%); p = 0.002), respectively, although it was well tolerated by all individuals and no medical assistance was required. DISCUSSION: 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.