PMID- 34373860 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240403 DP - 2021 Jul 30 TI - Correlates of Neutralizing/SARS-CoV-2-S1-binding Antibody Response with Adverse Effects and Immune Kinetics in BNT162b2-Vaccinated Individuals. LID - 2021.07.27.21261237 [pii] LID - 10.1101/2021.07.27.21261237 [doi] AB - 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: NT (50) ; 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 NT (50) s was seen in serums on day 28 post-1st dose. A moderate inverse correlation was seen between NT (50) s and ages, but no correlation was seen between NT (50) s and AEs. NT (50) s 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 (NT (50) s>1,500-fold: the top 4% among all participants' NT (50) s) potently to moderately blocked the infectivity of variants of concerns, some serums with moderate NT (50) s 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-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 (NT (50) s), determined by using infectious SARS-CoV-2 virions and live target cells, and adverse effects. Largely, NT (50) s and IgG levels were greater in women than in men. Following 28 days post-2 (nd) shot, significant reduction was seen in NT (50) s, IgG, and IgM levels. The average half-life of NT (50) s was approximately 68 days and the average time-length for participants' serums to lose the detectable activity was approximately 198 days. Although serums from elite-responders potently to moderately blocked the infectivity of variants of concerns, some serums with moderate NT (50) s 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 NT (50) s may fail to block beta variants. If BNT162b2-elicited immune memory is lost soon, additional vaccine(s) or other protective means would be needed. FAU - Maeda, Kenji AU - Maeda K AD - Department of Refractory Viral Infections, National Center for Global Health and Medicine (NCGM) Research Institute, Tokyo, Japan. FAU - Amano, Masayuki AU - Amano M AD - Department of Clinical Sciences, Kumamoto University Hospital, Kumamoto, Japan. FAU - Uemura, Yukari AU - Uemura Y AD - Department of Clinical Sciences, NCGM, Tokyo, Japan. FAU - Tsuchiya, Kiyoto AU - Tsuchiya K AD - AIDS Clinical Center, NCGM, Tokyo, Japan. FAU - Matsushima, Tomoko AU - Matsushima T AD - Sysmex Corporation, Hyogo, Japan. FAU - Noda, Kenta AU - Noda K AD - Sysmex Corporation, Hyogo, Japan. FAU - Shimizu, Yosuke AU - Shimizu Y AD - Department of Clinical Sciences, NCGM, Tokyo, Japan. FAU - Fujiwara, Asuka AU - Fujiwara A AD - Department of Refractory Viral Infections, National Center for Global Health and Medicine (NCGM) Research Institute, Tokyo, Japan. FAU - Takamatsu, Yuki AU - Takamatsu Y AD - Department of Refractory Viral Infections, National Center for Global Health and Medicine (NCGM) Research Institute, Tokyo, Japan. FAU - Ichikawa, Yasuko AU - Ichikawa Y AD - JCHO Kumamoto General Hospital, Kumamoto, Japan. FAU - Nishimura, Hidehiro AU - Nishimura H AD - JCHO Kumamoto General Hospital, Kumamoto, Japan. FAU - Kinoshita, Mari AU - Kinoshita M AD - JCHO Kumamoto General Hospital, Kumamoto, Japan. FAU - Matsumoto, Shota AU - Matsumoto S AD - JCHO Kumamoto General Hospital, Kumamoto, Japan. FAU - Gatanaga, Hiroyuki AU - Gatanaga H AD - AIDS Clinical Center, NCGM, Tokyo, Japan. FAU - Yoshimura, Kazuhisa AU - Yoshimura K AD - Tokyo Metropolitan Institute for Public Health, Tokyo, Japan. FAU - Oka, Shin-Ichi AU - Oka SI AD - AIDS Clinical Center, NCGM, Tokyo, Japan. FAU - Mikami, Ayako AU - Mikami A AD - Department of Clinical Sciences, NCGM, Tokyo, Japan. FAU - Sugiura, Wataru AU - Sugiura W AD - Department of Clinical Sciences, NCGM, Tokyo, Japan. FAU - Sato, Toshiyuki AU - Sato T AD - Sysmex Corporation, Hyogo, Japan. FAU - Yoshida, Tomokazu AU - Yoshida T AD - Sysmex Corporation, Hyogo, Japan. FAU - Shimada, Shinya AU - Shimada S AD - JCHO Kumamoto General Hospital, Kumamoto, Japan. FAU - Mitsuya, Hiroaki AU - Mitsuya H AD - Department of Refractory Viral Infections, National Center for Global Health and Medicine (NCGM) Research Institute, Tokyo, Japan. AD - Department of Clinical Sciences, Kumamoto University Hospital, Kumamoto, Japan. AD - Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. LA - eng PT - Preprint DEP - 20210730 PL - United States TA - medRxiv JT - medRxiv : the preprint server for health sciences JID - 101767986 UIN - Sci Rep. 2021 Nov 24;11(1):22848. PMID: 34819514 PMC - PMC8351777 COIS- Declaration of Interests Matsushima, Noda, Sato, and Yoshida are employees of Sysmex Corporation. EDAT- 2021/08/11 06:00 MHDA- 2021/08/11 06:01 PMCR- 2021/08/09 CRDT- 2021/08/10 06:40 PHST- 2021/08/10 06:40 [entrez] PHST- 2021/08/11 06:00 [pubmed] PHST- 2021/08/11 06:01 [medline] PHST- 2021/08/09 00:00 [pmc-release] AID - 2021.07.27.21261237 [pii] AID - 10.1101/2021.07.27.21261237 [doi] PST - epublish SO - medRxiv [Preprint]. 2021 Jul 30:2021.07.27.21261237. doi: 10.1101/2021.07.27.21261237.