A Comparative Scoping Review of Vaccine-Hesitancy Themes Across the COVID-19 Era, With Implications for Emerging mRNA Therapeutics

Abstract

Vaccine hesitancy has evolved substantially since the World Health Organization (WHO) first identified it as a global health threat in 2019. The COVID-19 pandemic accelerated this evolution by introducing messenger ribonucleic acid (mRNA) technology as a named, scrutinized object of public concern. As mRNA platforms now expand beyond infectious disease into cancer immunotherapy, with over 120 active clinical trials underway, understanding how hesitancy themes have shifted across time may help anticipate public reception of these emerging applications. This thesis examines vaccine hesitancy literature across three periods: pre-COVID-19, the COVID-19 pandemic era, and the post-pandemic declaration era, using a scoping review and qualitative content analysis of peer-reviewed sources identified through PubMed and Web of Science. Articles (N = 134) were coded thematically across twelve categories. Across the reviewed literature, hesitancy themes shifted in character over three periods. Before the pandemic, concerns centered on safety perceptions, parental autonomy, and policy-driven exemption debates. During the pandemic, attention turned to mechanism-specific fears, most notably the persistent misconception that mRNA vaccines alter human DNA, alongside the emergence of political identity as an independently studied predictor of hesitancy. After the pandemic, the literature showed distrust generalizing into routine childhood immunization, objections reframed around autonomy, and medical racism named more explicitly as a causal mechanism rather than merely a correlate. Across all three periods, racial and structural disparities rooted in historical medical mistreatment persisted as a durable theme distinct from biological literacy gaps. Because this study reflects patterns in a relevance-ranked, non-exhaustive literature sample rather than population-level survey data, these thematic shifts should be understood as changes in scholarly attention and framing– not as direct evidence of change in public attitudes. Building on these patterns, this thesis proposes a hypothesis-generating communication framework for emerging mRNA cancer therapeutics. It is organized around four response pathways: mechanistic misconception correction, transparent acknowledgment of genuine evidentiary gaps, institutional trust-building, and autonomy-affirming framing, intended to guide future empirical testing rather than to predict how the public will in fact receive these therapies.