Jay Belsky’s career has always focused on important social and behavioral challenges, and Jay specialized in showing how childhood experience shapes people’s behavior in the face of such challenges. Here we describe a project that could have been done by Jay himself, and that drew on ideas shared with us by Jay over the years of our friendship. The social problem we studied emerged from the 2020–21 COVID-19 pandemic: resistance to the vaccines. We carried out the project in the five-decade Dunedin Study, where we compared groups who differed in their intentions toward the COVID-19 vaccine in the weeks before vaccines became available. We found that vaccine-resistant and vaccine-hesitant cohort members had histories of adverse childhood experiences that fostered mistrust of authority, early-life mental-health problems that fostered misinterpretation of health messages, and early-life personality styles including tendencies to have extreme negative emotions, shut down mentally under stress, to value being a nonconformist, and to be fatalistic about health. Making matters worse, many Vaccine-Resistant and Vaccine-Hesitant participants also had difficulty cognitively comprehending health information. We found that negative vaccine intentions are not short-term misunderstandings that can be readily cleared up by delivering more information to adults in the midst of a public-health crisis. Instead they are part of a person’s lifelong psychological style of misinterpreting information and making unhealthy decisions during stressful uncertain situations. The key contribution from our study is the appreciation that this style is laid down well before secondary school age. To prepare for pandemics of the future, education about viruses and vaccines in schools could reduce citizens’ level of uncertainty and fear during a pandemic and give people preexisting knowledge that prevents shutdown under emotional distress and enhances their capacity to hear health messages.