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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

Abstract

Background

Emerging and future SARS-CoV-2 variants may jeopardize the effectiveness of vaccination campaigns. Therefore, it is important to know how the different vaccines perform against diverse SARS-CoV-2 variants.

Introduction

As of March 2022, the coronavirus disease 2019 (COVID-19) pandemic has caused over 458 million confirmed infections and over 6 million reported deaths [1], calling for strong interventions. A number of vaccines have been developed that proved efficacious in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the causative agent of COVID-19, and/or severe disease from infection, providing hope that we can halt this pandemic. Three vaccines, i.e. those developed by Pfizer-BioNTech (BNT162b2/Comirnaty), Moderna (mRNA-1273/Spikevax) and J&J/Janssen (Ad26.COV2.S), have been approved (for emergency use) in the United States by the FDA, while the EMA in the European Union has additionally approved (for emergency use) a fourth vaccine from Oxford/AstraZeneca (AZD1222/Vaxzevria), and very recently a fifth from Novavax (NVX-CoV2372/Nuvaxovid). Early efficacy trials showed that the mRNA vaccines BNT162b2 and mRNA-1273 had high efficacy (>90%) against symptomatic infection, whereas the adenovirus vector-based vaccines AZD1222 and Ad26.COV2.S resulted in lower vaccine efficacy (60–70%) against symptomatic infection [2–5]. Efficacy waned somewhat over time for all vaccines [6]. However, all vaccines were extremely effective at preventing severe disease. Neutralizing antibodies proved to be a very strong correlate of protection [7–10]. So far, over 10.7 billion COVID-19 vaccine doses have been administered worldwide [1].

Methods and Materials

Study design

Since March 2020, we followed a cohort of hospital health care workers (HCW) in the Amsterdam University Medical Centers, consisting of two tertiary care hospitals (S3 study, Netherlands Trial Register NL8645) [28]. This study is reported as per the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline (S1 Checklist). Participants underwent frequent phlebotomies to determine seroconversion against SARS-CoV-2, measured by total Ig against S1-RBD using enzyme-linked immunosorbent assay (Wantai ELISA). Between January and May 2021 participants of the cohort were vaccinated with either BNT162b2, mRNA-1273, AZD1222, or a single dose Ad.26CoV2.S (depending on the national distribution of available vaccines). Blood samples were taken approximately three weeks after the first vaccine with BNT162b2, mRNA-1273 and AZD1222 and four weeks after the second vaccine. In the case of vaccination with Ad.26CoV2.S, blood samples were taken approximately four to five and eight weeks after vaccination (Fig 1A). Preferably a blood sample was taken within days before the first vaccine was administered. Only seronegative HCW were included in the analysis. Between October 2021 and January 2022, the cohort was again invited for serum collection before and after BNT162b2 booster vaccination. Due to low attendance of the group vaccinated with mRNA-1273 or Ad26.COV2.S we included 16 additional SARS-CoV-2 naive HCW.

Results

Binding and neutralizing antibody responses after initial vaccination series

In a direct head-to-head comparison, using the same assays, we assessed the ability of four FDA and/or EMA approved SARS-CoV-2 vaccines to induce humoral immune responses in humans. From the S3 HCW cohort [53], we included SARS-CoV-2 naive individuals who completed BNT162b2 (n = 54), mRNA-1273 (n = 43), AZD1222 (n = 42) or Ad26.COV2.S vaccination (n = 26; S3 Table) and received a BNT162b2 booster vaccination. Although the four vaccine groups were fairly similar in composition, 65–86% female with the majority between 35–60 years old (Table 1), the AZD1222 group mostly consists of individuals over 60 years of age, because the Dutch government restricted the use of AZD1222 to this age group due to safety concerns. Furthermore, the Ad26.COV2.S group included fewer individuals because the Dutch government temporarily restricted its use because of similar reasons [54]. For vaccinees who received the BNT162b2, mRNA-1273 and AZD122 vaccines, samples were taken approximately three weeks after the first vaccination and four weeks after the second vaccination (Fig 1A). As the Ad26.COV2.S vaccine uses a single-dose regime, vaccine recipients were sampled approximately five and eight weeks after the single-dose vaccination. In addition, serum samples were collected pre- and four weeks post-BNT162b2 booster vaccination.

Discussion

Current and future SARS-CoV-2 variants could potentially jeopardize the effectiveness of vaccines in curbing the pandemic by escaping vaccine-induced immune responses. We present a direct comparison of the ability of four approved SARS-CoV-2 vaccines to induce neutralizing antibodies against VOCs, revealing that the mRNA vaccines are profoundly superior to the adenovirus vector-based vaccines at inducing neutralizing antibodies. We further show that the antibodies in SARS-CoV-2 vaccine recipients, sampled around the expected peak of their immunity, showed a marked decrease in neutralization potency against the VOCs, especially the Omicron variant, which was shown to form a separate antigenic cluster [64]. When neutralization activity against the original strain was limited, as observed after AZD1222 or Ad26.COV2.S vaccination, the capability to potently neutralize different variants is severely diminished. An mRNA booster significantly improved the neutralizing ability, including against the currently circulating Omicron variant.

Acknowledgments

We thank 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 donating cells and reagents for pseudovirus neutralization assays; Dirk Eggink and Chantal Reusken of the National Institute for Public Health and the Environment, Bilthoven, the Netherlands for providing the SARS-CoV-2 Delta and Omicron S proteins; Johan Reimerink, FionBrouwer, MariekeHoogerwerf and TarekMunawar, Bas J. Verkaik, Orlane J.A. Figaroa, Peter J. de Vries, Tessel M. Boertien, Neeltje A. Kootstra and all researchers, nurses and students of the RECoVERED Study team for technical assistance; Amsterdam UMC COVID-19 S3/HCW study group: Diederik van de Beek, Matthijs C. Brouwer, David T.P. Buis, Nora Chekrouni, Niels van Mourik, Sabine E. Olie, Edgar J.G. Peters, Yvo. M. Smulders, W. JoostWiersinga; and all the participants of the S3/HCW, COSCA and RECoVERED studies.

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. https://doi.org/10.1371/journal.pmed.1003991

Academic Editor: James G. Beeson, Burnet Institute, AUSTRALIA

Received: October 25, 2021; Accepted: April 18, 2022; Published: May 17, 2022

Copyright: © 2022 van Gils et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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

Funding: This work was supported by the Netherlands Organization for Scientific Research (NWO) ZonMw (Vici grant no. 91818627 to R.W.S., S3 study, grant agreement no. 10430022010023 to M.K.B.; RECoVERED, grant agreement no. 10150062010002 to M.D.d.J.), by the Bill & Melinda Gates Foundation (grant no. INV002022 and INV008818 to R.W.S. and INV-024617 to M.J.v.G.), by Amsterdam UMC through the AMC Fellowship (to M.J.v.G.) and the Corona Research Fund (to M.K.B.), and by the European Union’s Horizon 2020 program (RECoVER, grant no. 101003589 to M.D.d.J). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Amsterdam UMC filed a patent application on SARS-CoV-2 monoclonal antibodies including the ones used in this manuscript.

https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003991#ack

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