BACKGROUND: Vaccines fundamentally changed the course of the COVID-19 pandemic, saving >
14 million lives within a year. However, vaccine-conferred protection showed inter-individual variability, with many identified correlates of protection (e.g., age) not amenable to change. This prospective observational cohort study examined whether modifiable psychological factors (depressive symptoms, anxiety, perceived stress and positive mood), which predict antibody responses to other vaccines, also influenced the effectiveness of COVID-19 vaccines. We focussed on novel mRNA vaccines as these conferred greater clinical protection and psychological correlates have not been investigated in these vaccines previously. METHODS: One-hundred and eighty-four adults attending a mass-vaccination centre in the UK received a two-dose BNT162b2 mRNA SARS-CoV-2 vaccine course, completed validated psychological measures, and provided blood samples prior to vaccination and 4 weeks following the second vaccine dose. RESULTS: In separate linear regression models controlling for pre-vaccination antibody levels, demographic and clinical factors, higher levels of depressive symptoms (β = -0.15 [95 % CI: -0.30, -0.01], p = 0.041, partial f CONCLUSIONS: Lower levels of depressive symptoms and greater positive mood were associated with larger antibody responses following mRNA SARS-CoV-2 vaccination in a community sample attending for their first course of COVID-19 vaccinations. As both are amenable to change, they could offer mechanisms for enhancing vaccine effectiveness particularly among populations at greater risk of vaccine failure.