Time Since SARS-CoV-2 Infection and Humoral Immune Response Following BNT162b2 mRNA Vaccination

Brent Appelman,Jonne J Sikkens,Melissa Oomen,Rogier W Sanders,Meliawati Poniman,Judith A Burger,Lonneke A Van Vught,Michiel Schinkel,Marit J Van Gils,Joost Wiersinga,A.H Ayesha Lavell,Yvo M Smulders,Karlijn Van Der Straten,Marije Bomers,Alexander P J Vlaar,Marleen A Slim,Khadija Tejjani

doi:10.2139/ssrn.3844867

Abstract

Background: To optimise the use of available SARS-CoV-2 vaccines, some advocate delaying second vaccination for individuals infected within six months. We studied whether post-vaccination immune response is equally potent in individuals infected over six months prior to vaccination. Methods: We tested serum IgG binding to SARS-CoV-2 spike protein and neutralising capacity in 110 healthcare workers, before and after both BNT162b2 messenger RNA (mRNA) vaccinations. We compared outcomes between participants with more recent infection (n=18, median two months, IQR 2-3), with infection-vaccination interval over six months (n=19, median nine months, IQR 9-10), and to those not previously infected (n=73). Findings: Both recently and earlier infected participants showed comparable humoral immune responses after a single mRNA vaccination, while exceeding those of previously uninfected persons after two vaccinations with 2·5 fold (p=0·003) and 3·4 fold (p<0·001) for binding antibody levels, and 6·4 and 7·2 fold for neutralisation titers, respectively (both p<0·001). The second vaccine dose yielded no further substantial improvement of the humoral response in the previously infected participants (0·97 fold, p=0·92), while it was associated with a 4 fold increase in antibody binding levels and 18 fold increase in neutralization titers in uninfected participants (both p<0·001). Interpretation: Delaying the second vaccination in individuals infected up to ten months prior may constitute a more effective use of limited vaccine supplies. Funding Information: Netherlands Organization for Health Research and Development ZonMw; Corona Research Fund Amsterdam UMC; Bill & Melinda Gates Foundation. Declaration of Interests: All authors declare no conflict of interests. Ethics Approval Statement: The study was approved by institutional review boards of both hospitals, and written informed consent was obtained from each participant.

Highlights

Research in contextEvidence before this studyRecent studies show that a single messenger RNA (mRNA) vaccination in individuals with recent COVID-19 provides a potent immune response, equivalent to, or exceeding, the antibody response after two vaccinations in individuals without previous SARS-CoV-2- infection
We show that one dose of the BNT162b2 mRNA vaccine induces a humoral immune response in individuals previously infected with SARS-CoV-2 that exceeds antibody responses in uninfected individuals after two vaccine doses, even if the infection occurred more than six months prior
We included 110 participants who received their first vaccination with BNT162b2 (Pfizer-BioNTech) mRNA vaccine in January 2021, of whom 73 individuals were previously uninfected and 37 had a documented infection with SARS-CoV-2 in the past year. 8 out of 37 participants remained asymptomatic during infection

Summary

Introduction

Research in contextEvidence before this studyRecent studies show that a single mRNA vaccination in individuals with recent COVID-19 (up to six months prior) provides a potent immune response, equivalent to, or exceeding, the antibody response after two vaccinations in individuals without previous SARS-CoV-2- infection. Our study is the first to compare data of individuals with recent infection (within six months) to those infected over six months ago - and suggests a single mRNA vaccine in individuals infected up to ten months prior to vaccination is sufficient to elicit a potent humoral immune response. Findings: Both recently and earlier infected participants showed comparable humoral immune responses after a single mRNA vaccination, while exceeding those of previously uninfected persons after two vaccinations with 2.5 fold (p = 0.003) and 3.4 fold (p < 0.001) for binding antibody levels, and 6.4 and 7.2 fold for neutralisation titres, respectively (both p < 0.001). The second vaccine dose yielded no further substantial improvement of the humoral response in the previously infected participants (0.97 fold, p = 0.92), while it was associated with a 4 fold increase in antibody binding levels and 18 fold increase in neutralisation titres in previously uninfected participants (both p < 0.001).

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