Time since SARS-CoV-2 infection and humoral immune response following BNT162b2 mRNA vaccination

EBioMedicine. 2021 Oct:72:103589. doi: 10.1016/j.ebiom.2021.103589. Epub 2021 Sep 24.

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 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.

Keywords: BNT162b2; COVID-19; Humoral immune response; Neutralisation; SARS-CoV-2; Vaccine.

MeSH terms

  • Adult
  • Antibodies, Viral / blood*
  • Antibody Formation*
  • BNT162 Vaccine
  • COVID-19 Vaccines / pharmacology*
  • COVID-19 Vaccines / therapeutic use
  • COVID-19*
  • Female
  • Health Personnel
  • Humans
  • Immunity, Humoral
  • Immunoglobulin G / blood
  • Male
  • Middle Aged
  • Netherlands
  • Prospective Studies
  • SARS-CoV-2 / immunology*
  • Time Factors
  • Treatment Outcome

Substances

  • Antibodies, Viral
  • COVID-19 Vaccines
  • Immunoglobulin G
  • BNT162 Vaccine