Time since SARS-CoV-2 infection and humoral immune response following BNT162b2 mRNA vaccination
Brent Appelman,
Karlijn van der Straten,
A.H. Ayesha Lavell,
Michiel Schinkel,
Marleen A. Slim,
Meliawati Poniman,
Judith A. Burger,
Melissa Oomen,
Khadija Tejjani,
Alexander P.J. Vlaar,
W. Joost Wiersinga,
Yvo M. Smulders,
Lonneke A. van Vught,
Rogier W. Sanders,
Marit J. van Gils,
Marije K. Bomers,
Jonne J. Sikkens
Affiliations
Brent Appelman
Center for Experimental and Molecular Medicine, Amsterdam UMC, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands
Karlijn van der Straten
Department of Medical Microbiology, Amsterdam UMC, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands; Department of Internal Medicine, Amsterdam UMC, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands
A.H. Ayesha Lavell
Department of Internal Medicine, Amsterdam UMC, Amsterdam Institute for Infection and Immunity, Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam 1081 HV, the Netherlands
Michiel Schinkel
Center for Experimental and Molecular Medicine, Amsterdam UMC, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands; Department of Internal Medicine, Amsterdam UMC, Amsterdam Institute for Infection and Immunity, Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam 1081 HV, the Netherlands
Marleen A. Slim
Center for Experimental and Molecular Medicine, Amsterdam UMC, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands
Meliawati Poniman
Department of Medical Microbiology, Amsterdam UMC, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands
Judith A. Burger
Department of Medical Microbiology, Amsterdam UMC, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands
Melissa Oomen
Department of Medical Microbiology, Amsterdam UMC, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands
Khadija Tejjani
Department of Medical Microbiology, Amsterdam UMC, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands
Alexander P.J. Vlaar
Department of Intensive Care Medicine, Amsterdam UMC, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands
W. Joost Wiersinga
Department of Internal Medicine, Amsterdam UMC, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands
Yvo M. Smulders
Department of Internal Medicine, Amsterdam UMC, Amsterdam Institute for Infection and Immunity, Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam 1081 HV, the Netherlands
Lonneke A. van Vught
Center for Experimental and Molecular Medicine, Amsterdam UMC, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands; Department of Intensive Care Medicine, Amsterdam UMC, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands
Rogier W. Sanders
Department of Medical Microbiology, Amsterdam UMC, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, USA
Marit J. van Gils
Department of Medical Microbiology, Amsterdam UMC, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands
Marije K. Bomers
Department of Internal Medicine, Amsterdam UMC, Amsterdam Institute for Infection and Immunity, Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam 1081 HV, the Netherlands; Corresponding authors.
Jonne J. Sikkens
Department of Internal Medicine, Amsterdam UMC, Amsterdam Institute for Infection and Immunity, Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam 1081 HV, the Netherlands; Corresponding authors.
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 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). Adjustment for potential confounding of sex and age did not affect these findings. Interpretation: Delaying the second vaccination in individuals infected up to ten months prior may constitute a more efficient use of limited vaccine supplies. Funding: Netherlands Organization for Health Research and Development ZonMw; Corona Research Fund Amsterdam UMC; Bill & Melinda Gates Foundation.
