Psychological and Behavioral Determinants of Vaccine Efficacy: Insights from SARS-CoV-2 and Implications for Future Pandemics

Despite widespread vaccination, SARS-CoV-2 continues to circulate in waves, highlighting the need to better understand the multifactorial determinants of vaccine efficacy. Beyond its immediate health impact, the pandemic has intensified skepticism toward vaccines – a phenomenon with historical precedent dating back to Edward Jenner (1). Current hesitancy often arises from adverse effects, the accelerated pace of vaccine development, competition among pharmaceutical companies, and the proliferation of misinformation. While some concerns are evidence-based, many reflect perceived opacity from developers and political influence, as well as rumors.We hypothesize that negative attitudes toward vaccination may directly compromise immune responses. Psychological stress, anxiety, and depression can alter the neuroimmune axis, reducing both cellular and humoral immunity. This may partly explain suboptimal vaccine responses during COVID-19 and could influence outcomes in future pandemics.