Stratifying elicited antibody dynamics after two doses of SARS-CoV-2 vaccine in a community-based cohort in Fukushima, Japan

Recent studies have provided insights into the effect of vaccine boosters on recall immunity. Given the limited global supply of COVID-19 vaccines, identifying vulnerable populations with lower sustained vaccine-elicited antibody titers is important for targeting individuals for booster vaccinations. Here we investigated longitudinal data in a cohort of 2,526 people in Fukushima, Japan, from April 2021 to December 2021. Antibody titers following two doses of a COVID-19 vaccine were repeatedly monitored and information on lifestyle habits, comorbidities, adverse reactions, and medication use was collected. Using mathematical modeling and machine learning, we stratified the time-course patterns of antibody titers and identified vulnerable populations with low sustained antibody titers. Moreover, we showed that only 5.7% of the participants in our cohort were part of the “durable” population with high sustained antibody titers, which suggests that this durable population might be overlooked in small cohorts. We also found large variation in antibody waning within our cohort. There is a potential usefulness of our approach for identifying the neglected vulnerable population. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by Medical & Biological Laboratories Co., Ltd., Shenzhen YHLO Biotech Co., Ltd., the distributor and manufacturer of the antibody measurement system (iFlash 3000), Research Center for Advanced Science and Technology in the University of Tokyo, and in part by a National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2022R1C1C2003637) (to K.S.K.); a Grant-in-Aid for JSPS Scientific Research (KAKENHI) B 18H01139 (to S.I.), 16H04845 (to S.I.), Scientific Research in Innovative Areas 20H05042 (to S.I.); AMED CREST 19gm1310002 (to S.I.); AMED Development of Vaccines for the Novel Coronavirus Disease, 21nf0101638s0201 (to S.I.), 21nf0101638h0001 (to M.T.); AMED Japan Program for Infectious Diseases Research and Infrastructure, 20wm0325007h0001 (to S.I.), 20wm0325004s0201 (to S.I.), 20wm0325012s0301 (to S.I.), 20wm0325015s0301 (to S.I.); AMED Research Program on HIV/AIDS 22fk0410052s0401 (to S.I.); AMED Research Program on Emerging and Re-emerging Infectious Diseases 20fk0108140s0801 (to S.I.); AMED Program for Basic and Clinical Research on Hepatitis 21fk0210094 (to S.I.); AMED Program on the Innovative Development and the Application of New Drugs for Hepatitis B 22fk0310504h0501 (to S.I.); AMED Strategic Research Program for Brain Sciences 22wm0425011s0302; AMED JP22dm0307009 (to K.A.); JST MIRAI JPMJMI22G1 (to S.I.); Moonshot R&D JPMJMS2021 (to K.A. and S.I.) and JPMJMS2025 (to S.I.); Institute of AI and Beyond at the University of Tokyo (to K.A.); Mitsui Life Social Welfare Foundation (to S.I.); Shin-Nihon of Advanced Medical Research (to S.I.); Suzuken Memorial Foundation (to S.I.); Life Science Foundation of Japan (to S.I.); SECOM Science and Technology Foundation (to S.I.); The Japan Prize Foundation (to S.I.); Foundation of Kinoshita Memorial Enterprise (to S.I.); and Kowa Co (to M.T.). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The ethics committees of Hirata Central Hospital (number 2021-0611-1) and Fukushima Medical University (number 2021-116) gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors