Heterologous Vector—mRNA Based SARS-CoV-2 Vaccination Strategy Appears Superior to a Homologous Vector—Based Vaccination Scheme in German Healthcare Workers Regarding Humoral SARS-CoV-2 Response Indicating a High Boosting Effect by mRNA Vaccines

Abstract

Background: Longitudinal humoral SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) immunity for up to 15 months due to vaccination, the efficacy of vaccination strategies (homologous, vector–vector versus heterologous, vector–mRNA), the influence of vaccination side effects, and the infection rate in German healthcare workers need to be investigated. Methods: In this study, 103 individuals vaccinated against SARS-CoV-2 were enrolled to examine their anti-SARS-CoV-2 anti-N- and anti-RBD/S1-Ig levels. A total of 415 blood samples in lithium heparin tubes were prospectively obtained, and a structured survey regarding medical history, type of vaccine, and vaccination reactions was conducted. Results: All participants demonstrated a humoral immune response, among whom no values decreased below the positivity cutoff. Five to six months after the third vaccination, three participants showed anti-RBD/S1 antibodies of less than 1000 U/mL. We observed higher levels for heterologous mRNA-/vector-based combinations compared to pure vector-based vaccination after the second vaccination, which is harmonized after a third vaccination with the mRNA-vaccine only in both cohorts. The incidence of vaccine breakthrough in a highly exposed cohort was 60.3%. Conclusion: Sustained long-term humoral immunity was observed, indicating the superiority of a heterologous mRNA-/vector-based combination compared to pure vector-based vaccination. There was longevity of anti-RBD/S1 antibodies of at least 4 and up to 7 months without external stimulus. Regarding vaccination reactogenity, the occurrence of local symptoms as pain at the injection site was increased after the first mRNA application compared to the vector–vector cohort with a general decrease in adverse events at later vaccination time points. Overall, a correlation between the humoral vaccination response and vaccination side effects was not observed. Despite the high prevalence of vaccine breakthroughs, these only occurred in the later course of the study when more infectious variants, which are, however, associated with milder courses, were present. These results provide insights into vaccine-related serologic responses, and the study should be expanded using additional vaccine doses and novel variants in the future.

Vaccine-induced SARS-CoV-2 antibody response: the comparability of S1-specific binding assays depends on epitope and isotype discrimination

“…However, it is worth noting that our results are consistent with previous reports, as homologous prime-boost vaccination with ChAd-ChAd seems to result in lower antibody titers than vaccination with ChAd-BNT or BNT-BNT (TP5). These differences are almost equalized after the third vaccination with BNT (TP11; Supplementary Figure S7) (59)(60)(61)(62)(63).…”

The Impact of Clinical Factors and SARS-CoV-2 Variants on Antibody Production in Vaccinated German Healthcare Professionals Infected Either with the Delta or the Omicron Variant

“…As previously described [ 8 ], we used an electrochemiluminescence immunoassay (ECLIA) for the qualitative analysis of anti-SARS-CoV-2 anti-N Pan-Ig. This test had CE and FDA approval.…”

“…Moreover, we observed an emerging vaccine breakthrough previously, particularly with more contagious SARS-CoV-2 variants such as Omicron, in a prolonged observation period after vaccination [ 8 ]. In this context, the question arises whether higher infection rates are nevertheless associated with a more asymptomatic course.…”