key: cord-0880930-f2inw55s authors: Nishikimi, Akihiko; Watanabe, Ken; Watanabe, Atsushi; Yasuoka, Mikako; Watanabe, Ryota; Fujiwara, Mitsuhiro; Oshima, Hironori; Nakagawa, Takeshi; Kitagawa, Yuichi; Tokuda, Haruhiko; Washimi, Yukihiko; Niida, Shumpei; Kojima, Masayo title: Immune responses to COVID-19 vaccine BNT162b2 in workers at a research institute in Japan: 6-month follow-up survey date: 2022-05-20 journal: J Infect DOI: 10.1016/j.jinf.2022.05.016 sha: eb504164ad17107d32214560cd2c3e7eb6e82af5 doc_id: 880930 cord_uid: f2inw55s nan authors reported that the antibody levels markedly reduced between 3 and 6 months after the second dose. We also investigated the kinetics of S-IgG levels for 6 months after receiving the BNT162b2 (Pfizer-BioNTech) vaccine and the T-cell response among low responders in a cohort of workers at the National Center for Geriatrics and Gerontology, including a hospital and a research institute, in Japan. We have previously reported that seroprevalence against the nucleocapsid of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among our staff was equivalent to that observed among the local community and that 99.4% of the participants had S-IgG. 2, 3 However, the kinetics of the antibody titer against S-IgG after vaccination remain unclear. Additionally, T-cell-mediated cellular immunity may affect COVID-19 recovery, even with a low antibody response. 4 The relationship between humoral and cellular immune responses to vaccination has been rarely investigated. Of the 878 employees, 800 agreed to participate in the survey (participation rate: 91.1%). They received the first vaccination between February and June 2021 and the second dose 3 weeks later. Blood samples were obtained between June 14 and 18, 2021. This study was approved by the Institutional Review Board of the Ethics and Conflicts of Interest Committee (approval no 1481). All participants provided written informed consent. We performed all laboratory tests in-house using two S-IgG chemiluminescence enzyme immunoassays: the SARS-CoV-2 S-IgG from Sysmex and ARCHITECT SARS-CoV-2 IgG assay from Abbott. The positive cutoff value was 20 BAU/mL for Sysmex's and 50 AU/mL for Abbot's assays, respectively. The participants' characteristics are summarized in Table S1 (N = 800). The mean age ± SD was 41.0 ± 11.6 years, and 66. Of the 527 eligible participants who had received both vaccine doses by May 2021, all were positive for S-IgG except one participant. An age-dependent decline in antibody response was observed with Spearman correlation coefficient of -0.305 for the Sysmex tests (p < 0.001; Figure 1A ). Women tended to develop a higher S-IgG titer in each age group. The difference was significant in the age groups ≥51 years (Mann-Whitney U test with Bonferroni correction, p < 0.001), and the age difference was statistically significant regardless of sex (Kruskal-Wallis test, p < 0.001) ( Figure 1B) . The antibody titer tended to decline post-vaccination in a time-dependent manner, with a Spearman correlation coefficient of −0.325 (p < 0.001; Fig. 1C ). The median titer of samples collected 6-20 days after the second vaccination (n = 118) was 2,636 BAU/mL for the Sysmex test. Among the individuals who received the second dose 21-50 days before the survey (n = 512), the median antibody titers decreased to 1,599 BAU/mL. The antibody titer of participants who received the second dose >50 days before sample collection (n = 12) was reduced to 28.5%. Similar results were also obtained in the Abbott test ( Figure S1 ). Table S2 . A sharp decline in S-IgG titer was observed in the 6 months after receiving both vaccine doses (Figure 2A ). Median titers were reduced by 88.4% (from 2821 to 327 BAU/mL) for those who participated in the June survey 6-20 days at post-vaccination and by 88.9% (1537 to 172 BAU/mL) for those who participated at 21-50 days. However, most participants (n = 293, 98.7%) maintained a positive humoral immune response. Sex-dependent differences were not observed, whereas the titer significantly declined with age, with a Spearman correlation coefficient of −0.248 ( Figure 2B, C) . Consistent with the previous reports 1,5,6 , the anti-spike antibody titer resulting from mRNA vaccination was markedly reduced within a few months and continued to decline thereafter, suggesting the requirement of additional doses. Conversely, cellular responses, which remain broad to wild type and variants 7 , were maintained even at 5-6 months after the second dose in those who developed a sufficient antibody titer. A survey of larger cohorts in the future is warranted to confirm our observation. Immunogenicity of mRNA-1273 COVID vaccine after 6 months surveillance in health care workers; a third dose is necessary Seroprevalence of antibodies against SARS-CoV-2 among workers in a national research institute and hospital in Central Japan Prevalence of SARS-CoV-2 antibodies after one-year follow up among workers in a research institute in Japan CD8+ T cells contribute to survival in patients with COVID-19 and hematologic cancer Waning immune humoral response to BNT162b2 Covid-19 vaccine over 6 months Correlates of neutralizing/SARS-CoV-2-S1-binding antibody response with adverse effects and immune kinetics in BNT162b2-vaccinated individuals Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial The authors thank Shuji Nakamura, Junko Hirokawa, Megumi Banno, Yukari Kido, and Kanno Fujikawa for their technical assistance.