Comparative magnitude and persistence of SARS-CoV-2 vaccination responses on a population level in Germany

Abstract

BackgroundWhile SARS-CoV-2 vaccinations were successful in decreasing COVID-19 caseloads, recent increases in SARS-CoV-2 infections have led to questions about duration and quality of the subsequent immune response. While numerous studies have been published on immune responses triggered by vaccination, these often focused on the initial peak response generated in specific population subgroups (e.g. healthcare workers or immunocompromised individuals) and have often only examined the effects of one or two different immunisation schemes.Methods and FindingsWe analysed serum samples from participants of a large German seroprevalence study (MuSPAD) who had received all available vaccines and dose schedules (mRNA-1273, BNT162b2, AZD1222, Ad26.CoV2S.2 or a combination of AZD1222 plus either mRNA-1273 or BNT162b2). Antibody titers against various SARS-CoV-2 antigens and ACE2 binding inhibition against SARS-CoV-2 wild-type and the Alpha, Beta, Gamma and Delta variants of concern were analysed using a previously published multiplex immunoassay MULTICOV-AB and an ACE2-RBD competition assay. Among the different vaccines and their dosing regimens, homologous mRNA-based or heterologous prime-boost vaccination produced significantly higher antibody responses than vector-based homologous vaccination. Ad26.CoV2S.2 performance was significantly reduced, even compared to AZD1222, with 91.67% of samples being considered non-responsive forACE2 binding inhibition. mRNA-based vaccination induced a higher ratio of RBD- and S1-targeting antibodies than vector-based vaccination, which resulted in an increased proportion of S2-targeting antibodies. Previously infected individuals had a robust immune response once vaccinated, regardless of which vaccine they received. When examining antibody kinetics post-vaccination after homologous immunisation regimens, both titers and ACE2 binding inhibition peaked approximately 28 days post-vaccination and then decreased as time increased.ConclusionsAs one of the first and largest population-based studies to examine vaccine responses for all currently available immunisation schemes in Germany, we found that homologous mRNA or heterologous vaccination elicited the highest immune responses. The high percentage of non-responders for Ad26.CoV2.S requires further investigation and suggests that a booster dose with an mRNA-based vaccine may be necessary. The high responses seen in recovered and vaccinated individuals could aid future dose allocation, should shortages arise for certain manufacturers. Given the role of RBD- and S1-specific antibodies in neutralising SARS-CoV-2, their relative over-representation after mRNA vaccination may explain why mRNA vaccines have an increased efficacy compared to vector-based formulations. Further investigation on these differences will be of particular interest for vaccine development and efficacy, especially for the next-generation of vector-based vaccines.

Human serum from SARS-CoV-2-vaccinated and COVID-19 patients shows reduced binding to the RBD of SARS-CoV-2 Omicron variant

“…RBD binding and neutralization capacity do correlate [43,44]. The very low RBD binding in the Ad26.COV2.S compared to the COVID-19 patient group or the mRNA-vaccinated groups is in accordance with the former results [45] but impaired definite conclusions on Omicron immune escape upon Ad26.COV2.S vaccination. The reduced binding of sera from COVID-19 patients and mRNA vaccinees to the Omicron RBD was in accordance with our and other recent results [14-16, 46, 47] describing a highly reduced neutralization of the Omicron variant by human sera from vaccinated persons.…”

Cellular and Humoral Immune Response to a Third Dose of BNT162b2 COVID-19 Vaccine – A Prospective Observational Study

“…Contrarily, the administration of a heterologous-or a homologous mRNA strategy led to a stronger persistence. These discrepancies can be explained by the fact that Dulovic et al only examined persistence over a maximum period of 65 days following administration of the second vaccine dose (23). In our study, we considered a much longer time period of 6 months.…”

Cellular and humoral immune response to a third dose of BNT162b2 COVID-19 vaccine – a prospective observational study

“…Our data show that both humoral-and cellular immunity appear to be most persistent after examined persistence over a maximum period of 65 days following administration of the second vaccine dose [19]. In our study, we considered a much longer time period of 6 months.…”

“…Contrarily, the administration of a heterologous- or a homologous mRNA strategy led to a stronger persistence. These discrepancies can be explained by the fact that Dulovic et al only examined persistence over a maximum period of 65 days following administration of the second vaccine dose [19]. In our study, we considered a much longer time period of 6 months.…”