Differences in Immunogenicity of Three Different Homo- and Heterologous Vaccination Regimens against SARS-CoV-2

Abstract

Background: Due to findings on adverse reactions and clinical efficacy of different vaccinations against SARS-CoV-2, the administration of vaccination regimens containing both adenoviral vector vaccines and mRNA-based vaccines has become common. Data are still needed on the direct comparison of immunogenicity for these different regimens. Methods: We compared markers for immunogenicity (anti-S1 IgG/IgA, neutralizing antibodies, and T-cell response) with three different vaccination regimens (homologous ChAdOx1 nCoV-19 (n = 103), or mixture of ChAdOx1 nCoV-19 with mRNA-1273 (n = 116) or BNT162b2 (n = 105)) at two time points: the day of the second vaccination as a baseline and 14 days later. Results: All examined vaccination regimens elicited measurable immune responses that were significantly enhanced after the second dose. Homologous ChAdOx1 nCoV-19 was markedly inferior in immunogenicity to all other examined regimens after administration of the second dose. Between the heterologous regimens, mRNA-1273 as second dose induced greater antibody responses than BNT162b2, with no difference found for neutralizing antibodies and T-cell response. Discussion: While these findings allow no prediction about clinical protection, from an immunological point of view, vaccination against SARS-CoV-2 with an mRNA-based vaccine at one or both time points appears preferable to homologous vaccination with ChAdOx1 nCoV-19. Whether or not the demonstrated differences between the heterologous regimens are of clinical significance will be subject to further research.

Factors Influencing Antibody Response to SARS-CoV-2 Vaccination

“…The homologous vaccine regimen with ChAdOx resulted in a higher risk of being below the given threshold. This finding is in accordance with recent studies where this vaccine regimen led to a weaker immune response, whereas BNT162b2/BNT162b2 vaccines elicit a stronger antibody response [ 31 , 32 ]. Studies also showed that heterologous vaccines regimen mostly ChAdOx/BNT162b2 tend to have a stronger immunogenicity than homologous BNT162b2 regimen because of the additional effect of each vaccine on the humoral immune system response [ 31 , 33 ].…”

“…In our study, we saw that each administered vaccinations reduced the risk of being below the threshold. Time since vaccination is a widely known risk factor for waning antibodies levels [ 30 , 31 ], which was also demonstrated in our study.…”

Humoral Immune Response to CoronaVac in Turkish Adults

“…In contrast, others found anti-S1 IgG positivity in only 75.0–77.4% (Chile) [ 16 , 24 ]. The relevance of the second vaccine dose for eliciting markedly increased antibody titers has also been established for other COVID-19 vaccination regimens [ 25 , 26 , 27 ]. Compared to CoronaVac, both vector- and mRNA-based vaccines (e.g., ChAdOx1 and BNT162b2) elicit much higher anti-S1 titers and positivity rates already after the first vaccine dose.…”

The Effect of a Booster Dose mRNA Vaccine on COVID-19 Infection in Kidney Transplant Recipients after Inactivated or Viral Vector Vaccine Immunization

“…There were two strategies for using the booster dose vaccine: homologous (using the same vaccine platform) and heterologous (using a different vaccine platform) when compared to the previous two doses of the vaccination. Several studies have found that heterologous vaccines outperform homologous vaccines in terms of higher antibody production and T-cell activation in both the general population and KTRs [ 22 , 23 , 38 ]. The rate of seroconversion can be achieved in 60–70% of primary non-responders with a heterologous booster dose, leaving 20–25% of KTRs with no seroconversion after receiving a booster dose [ 15 , 16 , 39 ].…”