Comparing Heterologous and Homologous COVID-19 Vaccination: A Longitudinal Study of Antibody Decay

Abstract

The humoral response after vaccination was evaluated in 1248 individuals who received different COVID-19 vaccine schedules. The study compared subjects primed with adenoviral ChAdOx1-S (ChAd) and boosted with BNT162b2 (BNT) mRNA vaccines (ChAd/BNT) to homologous dosing with BNT/BNT or ChAd/ChAd vaccines. Serum samples were collected at two, four and six months after vaccination, and anti-Spike IgG responses were determined. The heterologous vaccination induced a more robust immune response than the two homologous vaccinations. ChAd/BNT induced a stronger immune response than ChAd/ChAd at all time points, whereas the differences between ChAd/BNT and BNT/BNT decreased over time and were not significant at six months. Furthermore, the kinetic parameters associated with IgG decay were estimated by applying a first-order kinetics equation. ChAd/BNT vaccination was associated with the longest time of anti-S IgG negativization and with a slow decay of the titer over time. Finally, analyzing factors influencing the immune response by ANCOVA analysis, it was found that the vaccine schedule had a significant impact on both the IgG titer and kinetic parameters, and having a Body Mass Index (BMI) above the overweight threshold was associated with an impaired immune response. Overall, the heterologous ChAd/BNT vaccination may offer longer-lasting protection against SARS-CoV-2 than homologous vaccination strategies.

Keywords: COVID-19; SARS-CoV-2; anti-Spike IgG response; antibody decay; heterologous vaccination.

Figure 1

Inter-group comparison of SARS-CoV-2 anti-trimeric Spike protein IgG among three different groups of immunized subjects at two, four and six months after vaccination. (A) All subjects (different number of patients reported in the figure). (B) Subgroup of subjects who completed the post-vaccination follow-up and whose blood samples showed a descending phase of the anti-S IgG concentration (n = 585). The box represents the interquartile range, and the whiskers extend to the lowest and highest value within 1.5 times the interquartile range from the hinges, respectively (Tukey-style). Kruskal Wallis test with Dunn’s post hoc multiple comparisons. * p ≤ 0.05; ** p ≤ 0.01; **** p ≤ 0.0001; ns = not statistically significant.

Figure 2

Kinetic analysis of IgG concentration decay following immunization with ChAd/ChAd (n = 124), BNT/BNT (n = 420) and ChAd/BNT (n = 41) among vaccinated subjects using a first-order kinetics equation: (A) time of negativization (t_neg), (B) rate constant k, (C) half-life (t_1/2). The box-whiskers are presented in Tukey style. Kruskal Wallis test with Dunn’s post hoc multiple comparisons. **** p ≤ 0.0001, ** p ≤ 0.01, ns = not statistically significant.