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AbstractTo design effective provaccination messaging, it is important to know "where people are coming from"—the personal experiences and long-standing values, motives, lifestyles, preferences, emotional tendencies, and information-processing capacities of people who end up resistant or hesitant toward vaccination. We used prospective data from a 5-decade cohort study, spanning childhood to midlife, to construct comprehensive early-life psychological histories of groups who differed in their vaccine intentions in months just before COVID vaccines became available in their country. Vaccine-resistant and vaccine-hesitant participants had histories of adverse childhood experiences that foster mistrust, longstanding mental-health problems that foster misinterpretation of messaging, and early-emerging personality traits including tendencies toward extreme negative emotions, shutting down mentally under stress, nonconformism, and fatalism about health. Many vaccine-resistant and -hesitant participants had cognitive difficulties in comprehending health information. Findings held after control for socioeconomic origins. Vaccine intentions are not short-term isolated misunderstandings. They are part of a person's style of interpreting information and making decisions that is laid down before secondary school age. Findings suggest ways to tailor vaccine messaging for hesitant and resistant groups. To prepare for future pandemics, education about viruses and vaccines before or during secondary schooling could reduce citizens' level of uncertainty during a pandemic, and provide people with pre-existing knowledge frameworks that prevent extreme emotional distress reactions and enhance receptivity to health messages. Enhanced medical technology and economic resilience are important for pandemic preparedness, but a prepared public who understands the need to mask, social distance, and vaccinate will also be important.