SARS-CoV-2 specific antibody response after an mRNA vaccine as the third dose: Homologous versus heterologous boost

Abstract

The aim of this study was to evaluate immunogenicity and longevity of the humoral immune response within six months after the homologous (BNT162b2/BNT162b2) or heterologous (BBIBP-CorV/BNT162b2) third dose, and to assess breakthrough infections among vaccinees during the Omicron wave in Serbia. Serum samples were analyzed at four timepoints: five months after the primary series; three weeks, three months, and six months after the boost. IgG antibodies against the receptor-binding domain of the spike protein were detected using enzyme-linked fluorescence assay. Both homologous (n = 55) and heterologous group (n = 36) showed a highly significant increase in antibody concentrations (p < 0.001) three weeks after the boost. A moderate inverse correlation between the age of recipients and the antibody levels at three weeks post-boost was observed in the homologous group (p = 0.02, r = −0.37), while the same correlation was not significant for heterologous group (p = 0.55, r = −0.15). Heterologous group had significantly higher antibody concentrations than homologous group at three weeks (Median 851.4(IQR 766.6–894.1); 784.3(676.9–847.4); p = 0.03) and three months post-boost (766.6(534.8–798.9); 496.8(361.6–664.0); p < 0.001). However, a significant decline in antibody response over time was noted for both strategies. The overall incidence of breakthrough cases was estimated at 36.36% (20/55) for homologous, and 16.67% (6/36) for heterologous group, but none of them required hospitalization. Although observed incidence in the homologous group was more than double when compared to the heterologous group, this difference was not statistically significant, most likely due to the small sample size. In conclusion, waning immunity after inactivated vaccine can be recovered by BNT162b2 heterologous boost regardless of the age of recipients, and both boost strategies induced potent humoral immune response and protection against severe COVID-19 during the Omicron wave. However, as the observed incidence of breakthrough infections was higher in the homologous group, although non-significant, this finding could indicate an advantage of heterologous approach.