Correlates of Neutralizing/SARS-CoV-2-S1-binding Antibody Response with Adverse Effects and Immune Kinetics in BNT162b2-Vaccinated Individuals
Authors: Maeda Kenji , Amano Masayuki , Uemura Yukari , Tsuchiya Kiyoto , Matsushima Tomoko , Noda Kenta , Shimizu Yosuke , Fujiwara Asuka , Takamatsu Yuki , Ichikawa Yasuko , Nishimura Hidehiro , Kinoshita Mari , Matsumoto Shota , Gatanaga Hiroyuki , Yoshimura Kazuhisa , Oka Shin-ichi , Mikami Ayako , Sugiura Wataru , Sato Toshiyuki , Yoshida Tomokazu , Shimada Shinya , Mitsuya Hiroaki 
Published: July 2021

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.

Research in context

Evidence before this study

While mRNA vaccines against SARS-CoV-2 have been exceedingly effective in preventing symptomatic viral infection, the salient features of immune response including the persistence of protection remain to be clarified. There is a report that anti-SARS-CoV-2 antibodies persist through 6 months after the second dose of mRNA-1273 vaccine (Doria-Roseet al. N Engl J Med. 2021;384:2259-2261); however, more definite immune kinetics following mRNA-vaccine-elicited protection have to be clarified. The mRNA-vaccine-elicited protection against SARS-CoV-2 variants are also to be determined.

Added value of this study

In the present prospective study, 225 twice-BNT162b2-dose-receiving individuals in Japan were enrolled. No significant correlation was seen between 50% neutralizing titers (NT50s), determined by using infectious SARS-CoV-2 virions and live target cells, and adverse effects. Largely, NT50s and IgG levels were greater in women than in men. Following 28 days post-2ndshot, significant reduction was seen in NT50s, IgG, and IgM levels. The average half-life of NT50s was ∼68 days and the average time-length for participants’ serums to lose the detectable activity was ∼198 days. Although serums from elite-responders potently to moderately blocked the infectivity of variants of concerns, some serums with moderate NT50s failed to block the infectivity of a beta strain.

Implications of all the available evidence

BNT162b2 efficacy is likely to be diminished to under detection limit by 6-7 months post-1stshot on average. Individuals with moderate NT50s may fail to block beta variants. If BNT162b2-elicited immune memory is lost soon, additional vaccine(s) or other protective means would be needed.