国立国際医療研究センター ワクチンの効果は最長で約半年。効果を維持するにはワクチン漬けにする必要。

 

Correlates of Neutralizing/SARS-CoV-2-S1-binding Antibody Response with Adverse Effects and Immune Kinetics in BNT162b2-Vaccinated Individuals

View ORCID ProfileKenji Maeda, Masayuki Amano, Yukari Uemura, Kiyoto Tsuchiya, Tomoko Matsushima, Kenta Noda, Yosuke Shimizu, Asuka Fujiwara, Yuki Takamatsu, Yasuko Ichikawa, Hidehiro Nishimura, Mari Kinoshita, Shota Matsumoto, Hiroyuki Gatanaga, Kazuhisa Yoshimura, Shin-ichi Oka, Ayako Mikami, Wataru Sugiura, Toshiyuki Sato, Tomokazu Yoshida, Shinya Shimada, Hiroaki Mitsuya

doi: https://doi.org/10.1101/2021.07.27.21261237

This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

SUMMARY

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.

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-Rose et 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-2^nd shot, 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-1^st shot 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.

Competing Interest Statement

Matsushima, Noda, Sato, and Yoshida are employees of Sysmex Corporation.

Funding Statement

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).

https://www.medrxiv.org/content/10.1101/2021.07.27.21261237v1

ワクチン漬けで免疫がバグりまくると・・・（爆ｗｗｗｗｗｗｗｗｗｗ