Abstract As we enter the fifth decade of the HIV pandemic, innovations in HIV vaccine research and development have moved us closer than ever to the availability of effective vaccines that could end HIV acquisition. Unfortunately, vaccine hesitancy (i.e., delay in acceptance or refusal of vaccination despite availability of vaccination services) poses a major threat to the future uptake of a proven vaccine. Globally, people of African descent have been disproportionately burdened by the HIV pandemic, facing higher morbidity and mortality. In the United States, the convergence of racism, mistrust in the healthcaresystem, inadequate community engagement,and concerns regarding vaccine literacy may exacerbate vaccine hesitancy, reducing future uptake within this population. To prepare for an inevitable HIV vaccine, including those with partial efficacy, we need to field-test targeted messaging campaigns that: are persuasive, counter vaccine-related myths and misinformation, come from trusted sources, and are culturally relevant and impactful. Moreover, campaigns must leverage digital platforms to which greater proportions of the population turn for critical health information. Guided by the Capability Opportunity Motivation—Behavior and Minority Health and Health Disparities Research Frameworks, this study will leverage participatory research methods, artificial intelligence, and infrastructure from ongoing HIV vaccine research at Duke University to: 1) Identify preferences regarding HIV vaccine attributes and communication strategies for African Americans in North Carolina using discrete choice experiments; 2) Develop and pilot crowdsourced and deep learning interventions to assess acceptability, feasibility, and preliminary impact on HIV vaccine literacy, confidence, and willingness; and 3) Evaluate the impact of a crowdsourced vs. a deep learning computer animation intervention on HIV vaccine literacy, confidence, and willingness to vaccinate compared to a control arm using a three-arm randomized experiment. The results of this study will: a) enable us to compare outcomes associated with community-driven, community-engaged, and expert-driven interventions to promote favorable attitudes towards an HIV vaccine; b) identify effective HIV vaccine promotion messages for African Americans; c) inform guidelines informing the rollout and promotion of future novel vaccines.