Coronavirus and other prevailing viruses continue to remain a health threat and challenge the efforts of institutions to promote vaccination acceptance. The current study’s aim is to propose a conceptual framework explaining the role of individual motivators (such as self-interest and collective interest) in shaping attitudes toward vaccination while emphasizing the pivotal role of institutional trust as a mediator and gender as a moderator. Data were collected via an online panel survey among Israelis (N = 464), and SEM statistics were used to test the model empirically. The path analysis model supports the positive direct effect of collective interest and the negative effect of self-interest. Additionally, it shows an indirect effect through the mediation effect of institutional trust and gender moderation. Therefore, institutional trust may significantly influence self-interest people’s attitudes toward vaccines. Furthermore, since females process information more comprehensively, their developed trustworthiness in institutions has an increased impact on vaccine acceptance. Theoretical and practical implications are discussed.