Objectives: SARS-CoV-2 remains a global health concern 3 years after its emergence. Safe and effective vaccines mitigate the pandemic impact, but the optimal schedule remains unclear, especially in a context where a high proportion of the population is infected. Methods: We periodically measured anti-spike SARS-CoV-2 immunoglobulin (Ig)G titers using a quantitative assay in an Israeli healthcare worker cohort who all received at least two BNT162b2 doses and either received further doses and/or were subsequently infected up to 22 months after dose two, and compared geometric mean concentrations according to number of doses received and infection status using analysis of variance. Results: Among the 993 included participants, infection after dose two led to higher geometric mean concentration IgG titers than a third dose (4285 vs 2845 arbitrary unit/ml 1-2 months after infection/vaccination, P = 0.03). In 16-18 months after dose two, those infected and those who received three or four vaccine doses all had IgG geometric mean concentration levels above 500 arbitrary unit/ml with no significant differences among groups (P = 0.6). IgG levels plateaued 16-22 months after dose two. Conclusion: Three BNT162b2 doses provide long-term immunogenicity comparable to breakthrough infection after dose two. Dose four transiently increases IgG levels and may be especially important for providing additional protection to vulnerable individuals during periods of increased transmission risk.
Bibliographical noteFunding Information:
This study was partially funded by the Russell Berrie Foundation through a non-committed research grant to Ziv Medical Centre. The funder played no role in study design, data collection, analysis, and interpretation of data, or the writing of this manuscript. The study has been conducted in accordance with International Conference on Harmonization (ICH) Guidelines on Good Clinical Practice (GCP) and applicable regulatory requirements consistent with the principles expressed in the Declaration of Helsinki. The study was approved by Ziv Medical Centre's ethics committee (0133-20-ZIV). ME, SZ, and KAJ conceptualized the study. ME, KAJ and KWB wrote the protocol. KWB, NB, and PB collected, managed, and curated the data. HBA and CS performed the laboratory assessments. ME analyzed the data. ME, KAJ, and KWB drafted the manuscript. The final manuscript was reviewed, edited, and approved for submission by all authors. Most data are available in the main text and appendixes. The anonymized minimum dataset is available upon written request to the corresponding author.
This study was partially funded by the Russell Berrie Foundation through a non-committed research grant to Ziv Medical Centre. The funder played no role in study design, data collection, analysis, and interpretation of data, or the writing of this manuscript.
© 2023 The Authors
ASJC Scopus subject areas
- Microbiology (medical)
- Infectious Diseases