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Antibody responses against SARS-CoV-2 variants induced by four different SARS-CoV-2 vaccines in health care workers in the Netherlands

Rogier W. Sanders ,Marit J. van Gils ,Ayesha Lavell ,Karlijn van der Straten ,Brent Appelman ,IljaBontjer,MeliawatiPoniman,Judith A. Burger,Melissa Oomen,Joey H. Bouhuijs,Lonneke A. van Vught,Marleen A. Slim,MichielSchinkel,ElkeWynberg,Rogier W. Sanders


Background: The emergence of new SARS-CoV-2 variants poses a threat to the effectiveness of vaccination efforts. Understanding how different vaccines perform against diverse variants is crucial in combating the ongoing COVID-19 pandemic.

Introduction: With over 458 million confirmed COVID-19 cases and 6 million reported deaths as of March 2022, the need for effective interventions is paramount. Several vaccines have been developed, such as Pfizer-BioNTech (BNT162b2/Comirnaty), Moderna (mRNA-1273/Spikevax), J&J/Janssen (Ad26.COV2.S), Oxford/AstraZeneca (AZD1222/Vaxzevria), and Novavax (NVX-CoV2372/Nuvaxovid). Early efficacy trials have shown high efficacy (>90%) of mRNA vaccines against symptomatic infection, while adenovirus vector-based vaccines exhibited lower efficacy (60-70%) [2-5]. Vaccine efficacy may decrease over time, but all vaccines have demonstrated effectiveness in preventing severe disease. Neutralizing antibodies have been identified as a strong correlate of protection [7-10]. Globally, over 10.7 billion COVID-19 vaccine doses have been administered [1].

Methods and Materials: A prospective cohort study was conducted on hospital health care workers (HCW) at Amsterdam University Medical Centers. The cohort received vaccinations with BNT162b2, mRNA-1273, AZD1222, or Ad26.COV2.S between January and May 2021. Blood samples were collected before and after vaccination to measure seroconversion against SARS-CoV-2 using enzyme-linked immunosorbent assay (ELISA). Additional serum samples were collected before and after a BNT162b2 booster vaccination between October 2021 and January 2022.

Results: The study compared the humoral immune responses induced by four approved SARS-CoV-2 vaccines in SARS-CoV-2 naive individuals. The mRNA vaccines (BNT162b2 and mRNA-1273) were found to be superior in inducing neutralizing antibodies compared to the adenovirus vector-based vaccines (AZD1222 and Ad26.COV2.S). Antibodies generated by AZD1222 or Ad26.COV2.S vaccination exhibited reduced neutralization potency against variants of concern (VOCs), particularly the Omicron variant. However, mRNA booster vaccination significantly improved neutralizing ability, including against the Omicron variant.

Discussion: The effectiveness of current and future SARS-CoV-2 vaccines could be compromised by emerging variants. This study demonstrates that mRNA vaccines elicit robust neutralizing antibody responses, while the neutralization ability of AZD1222 and Ad26.COV2.S vaccines against VOCs is substantially diminished. However, an mRNA booster vaccination enhances neutralization, including against the Omicron variant.

Acknowledgments: The authors express gratitude to Dr. Paul Bieniasz and Theodora Hatziioannou of the Howard Hughes Medical Institute, Rockefeller University, New York, USA, and Dr. Beatrice Hahn of the Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA, for their contributions. The authors also acknowledge various researchers, nurses, and students involved in the study.

Citation: van Gils MJ, Lavell A, van der Straten K, Appelman B, Bontjer I, Poniman M, et al. (2022) Antibody responses against SARS-CoV-2 variants induced by four different SARS-CoV-2 vaccines in health care workers in the Netherlands: A prospective cohort study. PLoS Med 19(5): e1003991.

Funding: The study received funding from the Netherlands Organization for Scientific Research (NWO) ZonMw, the Bill & Melinda Gates Foundation, Amsterdam UMC, and the European Union’s Horizon 2020 program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors declare the filing of a patent application on SARS-CoV-2 monoclonal antibodies by Amsterdam UMC.

Data Availability: All relevant data are included in the manuscript and its Supporting Information files.

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