Improving Vaccine Knowledge Among Adolescents: A Pre–Post School-Based Educational Intervention in Southern Italy

Background/Objectives: Vaccination coverage among adolescents remains below the recommended target, highlighting the need for effective educational strategies to improve vaccine knowledge. This study aimed to assess baseline knowledge of vaccines and immune mechanisms among adolescents and to evaluate whether a school-based educational intervention can improve knowledge related to vaccination. Methods: A prospective quasi-experimental pre–post study was conducted between 1 February 2025 and 1 June 2025 among adolescents aged 14–19 years attending high schools in Southern Italy. The intervention was based on the e-Bug educational module and delivered by trained nurses through interactive lessons, gamification, and guided discussions. Vaccine-related knowledge was assessed using a questionnaire administered before and after the intervention. Changes in knowledge scores were analyzed using paired statistical tests, and the effect size was estimated. A stepwise multivariate linear regression model was employed to identify factors associated with post-intervention test scores, with statistical significance set as p ≤ 0.05. Results: Among 386 participants, the majority were female (74.2%), the average age was 15.8, and 15% reported a chronic medical condition. Knowledge gaps were observed at baseline, particularly regarding the items on recommended adolescent vaccinations (37.4%), the definition of innate immunity (25.6%), and the mechanism of vaccines’ action (51%). After the intervention, all the items showed an improvement in correct answers, statistically significant for 5 of the 7 analyzed items (r = 0.364, p < 0.001). The most pronounced improvement was in the awareness of age-specific recommended vaccines (61.2%). The multivariate linear regression analysis showed that those with higher pre-intervention test scores, those who had parents with chronic medical conditions, those whose fathers worked, and those willing to participate in similar future interventions were more likely to achieve higher post-intervention test scores. Conclusions: School-based interventions may represent an effective strategy for enhancing adolescents’ knowledge related to vaccination, but further studies with control groups and long-term follow-up are needed to confirm effectiveness.