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.

NVX-CoV2373 induces humoral and cellular immune responses that are functionally comparable to vector and mRNA-based vaccines

“…All three vaccines showed high efficacy in preventing severe disease courses ( 3 – 5 ) and were also shown to mitigate the risk of long-term manifestation of COVID-19 ( 6 , 7 ). We and others could show in head-to-head comparisons that homologous and heterologous use of mRNA vaccines resulted in a significantly stronger humoral immune response and that was true after two ( 8 – 11 ) and also after three doses of vaccine ( 12 – 15 ). In contrast, results for T cell memories were not as clear cut with some descriptions of mRNA vaccines being superior to the homologous vector regimen ( 16 – 18 ), while others published comparable results for both vaccines ( 9 , 10 , 19 , 20 ).…”

Association between adverse events after COVID-19 vaccination and anti-SARS-CoV-2 antibody concentrations, the Netherlands, May 2021 to November 2022: a population-based prospective cohort study

“…Additionally, previous research has shown that those receiving heterologous vaccination compared with those receiving homologous vaccination had slower waning of antibodies [29]. As vaccine scheduling in regard to both dosing and vaccine product administered differed between countries [30], this might also explain why some studies reported an increase in AE after the second and third dose.…”

“…Antibody levels prior to a vaccination are influenced by the interval between previously administered vaccines or infection and vaccination, with longer dosing intervals between vaccinations possibly leading to higher antibody responses [ 28 ]. Additionally, previous research has shown that those receiving heterologous vaccination compared with those receiving homologous vaccination had slower waning of antibodies [ 29 ]. As vaccine scheduling in regard to both dosing and vaccine product administered differed between countries [ 30 ], this might also explain why some studies reported an increase in AE after the second and third dose.…”