Vaccine misinformation has posed a significant threat to public health. Drawing upon inoculation theory, this dissertation investigates whether exposure to an inoculation message – a message that forewarns and refutes potential persuasive attacks – can confer resistance to misinformation about COVID-19 vaccines. Based on two online experiments, this research seeks to answer four overarching questions: Can exposure to an inoculation message reduce susceptibility to misinformation? Through which mechanisms does inoculation message confer resistance to misinformation? Does the effect of inoculation messages vary among initially informed, uninformed, and misinformed individuals? How do partisan source cues (in-group vs. out-group) impact the effectiveness of inoculation messages among politically affiliated individuals? Study 1 investigated the effectiveness, mechanisms, and recipient factors related to inoculation messages. A two-condition (inoculation vs. control) between-subject experiment was conducted (N = 659). Results indicated that exposure to an inoculation message effectively reduced individuals' susceptibility to misinformation. Inoculation message not only counteracted beliefs in misinformation but also protected positive attitudes and intentions toward COVID-19 vaccination. Moreover, perceived ease of counterarguing and anger were identified as significant mediators underlying the persuasive effects of the inoculation message, while counterarguing was not a significant mediator. Furthermore, the effectiveness of inoculation message remained consistent among initially informed, uninformed, or misinformed groups, suggesting that inoculation message offers both prophylactic and therapeutic effects. Study 2 examined how partisan source cues impacted inoculation message effectiveness. A 2 (in-group vs. out-group inoculation) X 2 (in-group vs. out-group misinformation) between-subject online experiment was conducted among politically affiliated individuals (N = 448). Results showed no main or interaction effects of in-group (vs. out-group) inoculation and in-group (vs. out-group) misinformation on persuasive outcomes, suggesting that the efficacy of inoculation messages in conferring resistance to misinformation did not differ based on whether the inoculation or misinformation messages came from an in-group or out-group source. Additionally, party identification strength moderated the impact of in-group (vs. out-group) inoculation on beliefs in COVID-19 vaccine misinformation and COVID-19 vaccination attitudes. Surprisingly, the advantage of in-group inoculation over out-group inoculation was stronger among individuals with lower levels of party identification. Moreover, out-group inoculation appeared to be more persuasive than in-group inoculation among individuals with extremely strong political identification. This dissertation offers several theoretical and practical implications for health communication research and practice. First, this research contributes to inoculation theory by examining two alternative mechanisms – perceived ease of counterarguing and anger – underlying inoculation message effects. The findings underscore the importance of considering cognitive, meta-cognitive, and affective routes that underlie resistance to persuasion. Additionally, this research expands the scope of inoculation theory by demonstrating its effectiveness among initially informed, uninformed, and misinformed individuals. These results suggest that inoculation messages can be useful beyond the traditional scope of cultural truisms, offering both prophylactic and therapeutic effects. Furthermore, the study challenges the conventional assumption that messages from in-group sources are more persuasive than those from out-group sources, indicating that political groups should work together to address vaccine hesitancy. Overall, this dissertation supports the use of inoculation messages as an effective tool in counteracting misinformation and promoting vaccination acceptance.