Vaccine hesitancy is still a significant barrier to achieving widespread immunity in many communities. In this paper, we evaluated a serious game focusing on vaccination against COVID-19. This study investigates the potential of virtual reality (VR) as an innovative educational tool to address this issue. Focusing on the serious game “Spike Force”, which simulates the mechanisms of the mRNA COVID-19 vaccine, this research evaluates the game’s effectiveness in enhancing participants’ understanding, altering attitudes, and influencing behaviours related to vaccination. Participants engaged with “Spike Force,” and their knowledge, attitudes, and behaviours were assessed through pre- and post-gameplay questionnaires. The findings show that immersive VR experiences can significantly improve vaccine literacy, increase confidence in vaccine-related discussions, and promote positive behavioural changes toward vaccination. These results suggest that VR could play an effective advocacy role for public health education, particularly in combating vaccine hesitancy.