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Background: Herd immunity or community immunity refers to the reduced risk of infection among susceptible individuals in a population through the presence and proximity of immune individuals. Recent studies suggest that improving the understanding of community immunity may increase intentions to get vaccinated., Objective: This study aims to design a web application about community immunity and optimize it based on users' cognitive and emotional responses., Methods: Our multidisciplinary team developed a web application about community immunity to communicate epidemiological evidence in a personalized way. In our application, people build their own community by creating an avatar representing themselves and 8 other avatars representing people around them, for example, their family or coworkers. The application integrates these avatars in a 2-min visualization showing how different parameters (eg, vaccine coverage, and contact within communities) influence community immunity. We predefined communication goals, created prototype visualizations, and tested four iterative versions of our visualization in a university-based human-computer interaction laboratory and community-based settings (a cafeteria, two shopping malls, and a public library). Data included psychophysiological measures (eye tracking, galvanic skin response, facial emotion recognition, and electroencephalogram) to assess participants' cognitive and affective responses to the visualization and verbal feedback to assess their interpretations of the visualization's content and messaging., Results: Among 110 participants across all four cycles, 68 (61.8%) were women and 38 (34.5%) were men (4/110, 3.6%; not reported), with a mean age of 38 (SD 17) years. More than half (65/110, 59.0%) of participants reported having a university-level education. Iterative changes across the cycles included adding the ability for users to create their own avatars, specific signals about who was represented by the different avatars, using color and movement to indicate protection or lack of protection from infectious disease, and changes to terminology to ensure clarity for people with varying educational backgrounds. Overall, we observed 3 generalizable findings. First, visualization does indeed appear to be a promising medium for conveying what community immunity is and how it works. Second, by involving multiple users in an iterative design process, it is possible to create a short and simple visualization that clearly conveys a complex topic. Finally, evaluating users' emotional responses during the design process, in addition to their cognitive responses, offers insights that help inform the final design of an intervention., Conclusions: Visualization with personalized avatars may help people understand their individual roles in population health. Our app showed promise as a method of communicating the relationship between individual behavior and community health. The next steps will include assessing the effects of the application on risk perception, knowledge, and vaccination intentions in a randomized controlled trial. This study offers a potential road map for designing health communication materials for complex topics such as community immunity., (©Hina Hakim, Julie A Bettinger, Christine T Chambers, S Michelle Driedger, Eve Dubé, Teresa Gavaruzzi, Anik M C Giguere, Éric Kavanagh, Julie Leask, Shannon E MacDonald, Rita Orji, Elizabeth Parent, Jean-Sébastien Paquette, Jacynthe Roberge, Beate Sander, Aaron M Scherer, Martin Tremblay-Breault, Kumanan Wilson, Daniel Reinharz, Holly O Witteman. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 30.10.2020.)