Available online 28 February 2024, 105661

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mRNA-1273 booster vaccination induces higher increase of RBD-antibody levels

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superiority of mRNA-1273 is independent of primary vaccination strategy

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no differences in safety between mRNA-1273 and BNT162b2 was observed

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Neutralizing antibody titres highly correlated with anti-RBD antibodies

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Neutralizing capacity is 4.4 fold higher against wild type compared to Omicron

ABSTRACTBackground

Various SARS-CoV-2 variants of concerns (VOCs) characterized by higher transmissibility and immune evasion have emerged. Despite reduced vaccine efficacy against VOCs, currently available vaccines provide protection. Population-based evidence on the humoral immune response after booster vaccination is crucial to guide future vaccination strategies and in preparation for imminent COVID-19 waves.

Methods

This multicenter, population-based cohort study included 4,697 individuals ≥18 years of age who received a booster vaccination. Antibody levels against SARS-CoV-2 receptor binding domain (RBD) and neutralizing antibodies against wild-type (WT) virus and Omicron variants were assessed at baseline (day of booster vaccination) and after four weeks. Safety was evaluated daily within the first week using a participant-completed electronic diary. Antibody levels were compared across different vaccination strategies, taking into account individual host factors.

Results

Our main model including 3,838 participants revealed that individuals who received a booster with mRNA-1273 compared to BNT162b2 vaccine had a significantly higher increase (95%CI) in anti-RBD-antibody levels (37,707 BAU/mL [34,575 – 40,839] vs. 27,176 BAU/mL [26,265 – 28,087]), and of neutralization levels against WT (1,681 [1,490 – 1,872] vs. 1,141 [1,004 – 1,278] and Omicron variant (422 [369 - 474] vs. 329 [284 - 374]). Neutralizing antibody titres highly correlated with anti-RBD antibodies, with neutralizing capacity 4.4 fold higher against WT compared to Omicron. No difference in safety were found between the two booster vaccines.

Conclusion

Our study underlines the superiority of a booster vaccination with mRNA-1273, independent of the primary vaccination and therefore provides guidance on the vaccination strategy.

Section snippetsINTRODUCTION

Vaccination is an important mitigation strategy to prevent transmission of SARS-CoV-2 infection and immunized individuals additionally show a reduced risk of severe disease courses compared to non-vaccinated persons. (1)

COVID-19 vaccines induce the production of antibodies against the spike (S) protein, which can be quantified by receptor binding domain (RBD)-specific immunoassays to assess the humoral immune response to vaccination. Antibody waning, the appearance of variants, and an

Study design and study population

This prospective, open-label clinical cohort study on immunogenicity and safety of COVID-19 booster vaccinations in Vienna, Austria was initiated on October 28th 2021, and the last participant's first visit was on January 21st 2022. It was conducted at the Austria Centre Vienna and the Medical-University-Vienna located at the Vienna-General-Hospital including 5,000 adults (≥18 years) who had received primary immunization against COVID-19 according to national guidelines at least 4 months prior

Patient characteristics

In total, 4,697 participants were included in the study of which 402 individuals were lost to follow-up. After excluding individuals with missing on main variables (n=72) and history of COVID-19 infection (n=385) 3,838 participants were included for further analyses (Figure 1). The majority of the study population received BNT162b2 (n= 3,288) as booster vaccination, the remainder mRNA-1273 (n=550). Baseline characteristics of the cohort are displayed in Table 1, and grouped by vaccination

DISCUSSION

In this large, population-based study, representing a real-world vaccination campaign in Central Europe, we investigated the humoral immune response after COVID-19 booster vaccination with either BNT162b2 or mRNA-1273. Our main models revealed that mRNA-1273 booster induces not only quantitatively higher antibody levels, but also higher functionality of antibodies, as determined by assessing the neutralizing capacity against WT and Omicron. Notably, the highest increase in antibody levels were

CRediT authorship contribution statement

Daniela Sieghart: Conceptualization, Investigation, Methodology, Project administration, Writing – original draft, Writing – review & editing, Funding acquisition. Claudia A. Hana: Data curation, Formal analysis, Methodology, Writing – original draft. Caroline Dürrschmid: Data curation, Investigation, Project administration, Writing – original draft, Writing – review & editing. Leonhard X Heinz: Methodology, Visualization, Writing – review & editing. Helmuth Haslacher: Conceptualization,

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

I hereby confirm that all authors have stated no known competing financial, commercial or personal interests.

Daniel Aletaha

Acknowledgment Section

We thank all the individuals who participated. We thank Stefan Jakovlevic, Jelena Milovanovic, Valentin Marzoner, Ece Danisman, Lukas Schulz, Sebastian Habernig, Philip Nasztl, Paul Helbig, Maria Weber, Sarah Ely, and Sabine Schranz, for their support. We thank Birgit Niederreiter, Manuela Repl, and Astrid Radakovics for their technical assistance. We thank Alan Abdulkarim, Ihor Shulym and Thomas Wrba for their IT support.

Funding source

The study was funded by the Federal Ministry of Education, Science and Research of the Republic of Austria; the City of Vienna; and the Medical Scientific Fund of the Mayor of the City of Vienna (Project number 21226). The funding source did not influence study design, conduct or reporting.

Ethical statement

The clinical trial (Eudra-CT: 2021-005094-28) was approved on the 21st of October 2022 by the local ethical committee of the Medical University of Vienna as well as the ethical committee of the City of Vienna with the ethical protocol number 1954/2021. All participants gave informed written consent.

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© 2024 Published by Elsevier B.V.