Correlates of Neutralizing/SARS-CoV-2-S1-Binding Antibody Response With Adverse Effects and Immune Kinetics in BNT162b2-Vaccinated Individuals (preprint)

ABSTRACT

Background: While mRNA vaccines against SARS-CoV-2 have been exceedingly effective in preventing symptomatic viral infection, the features of immune response remain to be clarified.Methods: In the present prospective observational study, 225 healthy individuals in Kumamoto General Hospital, Japan, who received two BNT162b2 doses in February 2021, were enrolled. Correlates of BNT162b2-elicited SARS-CoV-2-neutralizing activity (50% neutralization titer NT50; assessed using infectious virions and live target cells) with SARS-CoV-2-S1-binding-IgG and -IgM levels, adverse effects (AEs), ages, and genders were examined. The average half-life of neutralizing activity and the average time length for the loss of detectable neutralizing activity were determined and the potency of serums against variants of concerns was also determined.Findings: Significant rise in NT50s was seen in serums on day 28 post-1st dose. A moderate inverse correlation was seen between NT50s and ages, but no correlation was seen between NT50s and AEs. NT50s and IgG levels on day 28 post-1st dose and pain scores following the 2nd shot were greater in women than in men. The average half-life of neutralizing activity in the vaccinees was approximately 67.8 days and the average time length for their serums to lose the detectable neutralizing activity was 198.3 days. While serums from elite-responders (NT50s >1,500-fold the top 4% among all participants’ NT50s) potently to moderately blocked the infectivity of variants of concerns, some serums with moderate NT50s failed to block the infectivity of a beta strain.Interpretation: BNT162b2-elicited immune response has no significant association with AEs. BNT162b2-efficacy is likely diminished to under detection limit by 6-7 months post-1st shot. High-level neutralizing antibody-containing serums potently to moderately block the infection of SARS-CoV-2 variants; however, a few moderate-level neutralizing antibody-containing serums failed to do so. If BNT162b2-elicited immunity memory is short, an additional vaccine or other protective measures would be needed.Funding Information This research was supported in part by a grant from the Japan Agency for Medical Research and Development to Maeda (grant number JP20fk0108260, 20fk0108502) and to Mitsuya (grant number 20fk0108502), and in part by a grant for MHLW Research on Emerging and Re-emerging Infectious Diseases and Immunization Program to Maeda (grant number JPMH20HA1006) from Ministry of Health, Labor and Welfare, and in part by a grant for COVID-19 to Mitsuya (grant number 19A3001) and Maeda (grant number 20A2003D) from the Intramural Research Program of National Center for Global Health and Medicine, and in part by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health (Mitsuya).Declaration of Interests Matsushima, Noda, Sato, and Yoshida are employees of SysmexCorporation.Other authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.Ethics Approval Statement The Ethics Committees from the Kumamoto General Hospital and NCGM approved this study (Kumamoto General Hospital No. 180, and NCGM-G-004176-00, respectively). Each participant provided a written informed consent, and this study abided by the Declaration of Helsinki principles.