BNT162b2 Vaccine-Induced Immune Responses and Dynamics Vary Among Age Groups, Sex and Co-Morbidities: A Longitudinal Prospective Cohort Study

Background: Concurrent to BNT162b2 vaccine rollout in Israel, we performed a longitudinal prospective cohort study to assess the early antibody response and antibody kinetics after each vaccine dose among health care workers (HCW) of different ages, gender and co-morbidities.    Methods: Overall 2,607 vaccinated HCW were followed for five weeks after vaccination and Immunoglobulin (Ig)M, IgA, IgG and neutralizing antibodies were measured by Beckman-coulter SARS-CoV-2 RBD IgG, ELISA-RBD and pseudo-virus neutralization assays. Scatter plot and correlation analyses, logistic and linear regression analyses and linear mixed models were used to investigate the longitudinal antibody response. Findings: The first vaccine dose elicited low IgG and neutralizing antibody response in the majority of HCW which were rapidly induced 10 and 32 folds, respectively following the second vaccine dose. High (r=0.92) correlation was detected between IgG and neutralizing titers. First dose induced IgG response was significantly lower in older (>65, Ratio of means=0.25 95%CI 0.19-0.31) and immunosuppressed (0.21 95%CI 0.14-0.31) individuals. Yet, this was partially abrogated following the second dose. Overall, lower antibody levels were consistently associated with males (0.84 95%CI 0.80-0.89), older age (>65, 0.64 95%CI 0.58-0.71), immunosuppression (0.44 95%CI 0.33-0.58), and other specific comorbidities (diabetes (0.88 95%CI 0.79-0.98), hypertension (0.90 95%CI 0.82-0.98), heart disease (0.86 95%CI 0.75-0.99) and autoimmune diseases (0.82 95%CI 0.73-0.92). Interpretation: BNT162b2 vaccine induces a strong and rapid antibody response. The significant correlation between IgG antibodies and neutralization titers, suggest that IgG antibodies may serve as a correlate of neutralization. The second vaccine dose is significantly more important for older and immunosuppressed individuals. Antibody responses were reduced in vulnerable populations and therefore they may be more prone to breakthrough infections.  Declaration of interests: None to declare. Ethics statement: The protocol and informed consent were approved by the Institutional review 125 board of the Sheba Medical Center. Written informed consent was obtained from all 126 participants. Funding: MOH and Sheba medical Center, Israel