Abstract
Recent increases in SARS-CoV-2 infections have led to questions about duration and quality of vaccine-induced immune protection. While numerous studies have been published on immune responses triggered by vaccination, these often focus on studying the impact of one or two immunisation schemes within subpopulations such as immunocompromised individuals or healthcare workers. To provide information on the duration and quality of vaccine-induced immune responses against SARS-CoV-2, we analyzed antibody titres against various SARS-CoV-2 antigens and ACE2 binding inhibition against SARS-CoV-2 wild-type and variants of concern in samples from a large German population-based seroprevalence study (MuSPAD) who had received all currently available immunisation schemes. We found that homologous mRNA-based or heterologous prime-boost vaccination produced significantly higher antibody responses than vector-based homologous vaccination. Ad26.CoV2S.2 performance was particularly concerning with reduced titres and 91.7% of samples classified as non-responsive for ACE2 binding inhibition, suggesting that recipients require a booster mRNA vaccination. While mRNA vaccination induced a higher ratio of RBD- and S1-targeting antibodies, vector-based vaccines resulted in an increased proportion of S2-targeting antibodies. Given the role of RBD- and S1-specific antibodies in neutralizing SARS-CoV-2, their relative over-representation after mRNA vaccination may explain why these vaccines have increased efficacy compared to vector-based formulations. Previously infected individuals had a robust immune response once vaccinated, regardless of which vaccine they received, which could aid future dose allocation should shortages arise for certain manufacturers. Overall, both titres and ACE2 binding inhibition peaked approximately 28 days post-second vaccination and then decreased.
Highlights
In response to the global SARS-CoV-2 pandemic, multiple vaccines have been developed, tested and licensed for use within record time [1–4]
Using MULTICOV-AB, we compared vaccinationinduced antibody titres generated against the full-length Spike trimer, RBD, S1 and S2 domains and found that mRNA-based homologous vaccinations induced a greater Spike, RBD and S1 response than vector-based ones (Figure 1)
Heterologous dose vaccination schemes resulted in comparable titres as homologous mRNA vaccine regimens among our study group independent of the origin of the second dose (Spike normalised median fluorescence intensity (MFI): AZD1222-mRNA-1273 13.59, AZD1222-BNT162b2 13.27, RBD normalised MFI: AZD1222mRNA-1273 28.17, AZD1222-BNT162b2 25.93)
Summary
In response to the global SARS-CoV-2 pandemic, multiple vaccines have been developed, tested and licensed for use within record time [1–4]. Individuals who had received a first dose of AZD1222 and were below the age of 60 were instead offered a mRNA-based vaccine as second dose which resulted in a heterologous primeboost vaccination scheme [18]. These “mix and match” approaches were not covered by the initial licensing terms, it has been shown that they result in a more robust humoral and cell-mediated immune response compared to the homologous AZD1222 immunisation [19, 20]. By using samples from a population-based seroprevalence study (MuSPAD), which assessed SARS-CoV-2 seroprevalence from July 2020 to August 2021 in eight regions in Germany [27], we examined the dynamics of vaccine-induced humoral responses using MULTICOV-AB [28] and an ACE2-RBD competition assay [29] to analyze ACE2 binding inhibition
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