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

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.