BackgroundResearch characterizing changes of heart with respect to vaccine intention is scarce, and very little research considers those who were initially vaccine willing but became hesitant. Here, we sought to assess the factors related to reversals of vaccine willingness.MethodsWe conducted a longitudinal, national survey on vaccination intention among Japanese adults aged 20 years or older, with the first questionnaire performed in February-March 2021 (N = 30,053) and the follow-up in February 2022 (N = 19,195, response rate 63.9%). The study population comprised those who reported vaccine willingness in the first survey, with the outcome variable being development of vaccine hesitancy at follow-up. We performed a regression analysis of vaccination status using sociodemographic, health-related, psychologic/attitudinal, and information-related variables as predictors. We used the sparse group minimax concave penalty (MCP) to select the optimum group of covariates for the logistic regression.FindingsOf 11,118 (57.9%) respondents who previously expressed interest in vaccination, 10,684 (96.1%) and 434 (3.9%) were in the vaccine willing and hesitant groups, respectively. Several covariates were found to significantly predict vaccine hesitancy, including marital status, influenza vaccine history, COVID-19 infection/testing history, engagement in COVID-19 preventive measures, perceived risks/benefits of the COVID-19 vaccine, and attitudes regarding vaccination policies and norms. The use of certain information sources was also associated with vaccine hesitancy.InterpretationSociodemographic, health-related, psychologic/attitudinal, and information-related variables predicted the development of vaccine hesitancy among those with prior willingness. Most of these predictors were also associated with vaccination status.FundingThe present work was supported in part by a grant from the Kanagawa Prefectural Government of Japan and by AIST government subsidies.