Background <p>Ghana’s vaccine research ecosystem has evolved substantially alongside national and global immunisation efforts. However, the extent and distribution of research activity across the full vaccine development continuum have not been systematically synthesised. This review maps peer-reviewed publications and institutional reports across a nine-stage vaccine development framework from 1977 to 2025, comparing patterns between the pre-pandemic (2000–2020) and post-pandemic (2021–2025) periods.</p> Main body <p>Before 2020, vaccine-related research in Ghana was concentrated predominantly in downstream domains, including disease surveillance, programme implementation, and Phase II–III clinical trials, with notable contributions to malaria and pneumococcal vaccine development. Following the COVID-19 pandemic, publication output increased more than fivefold and diversified into emerging areas such as genomic surveillance, regulatory science, behavioural research, and digital health systems, accompanied by stronger leadership from domestic institutions. Despite this expansion, engagement in upstream domains, including discovery science, preclinical development, Phase I clinical trials, and local vaccine manufacturing, remains limited, reflecting persistent structural and infrastructure constraints.</p> Conclusions <p>Ghana has transitioned from a primarily implementation-focused setting to an increasingly active contributor to multidisciplinary vaccine evidence. Sustained investment in upstream research infrastructure, early-phase clinical trial capacity, sustainable financing mechanisms and behavioural intervention research will be essential to strengthen national vaccine sovereignty. The Ghanaian experience offers transferable lessons for other low- and middle-income countries seeking to build resilient and locally driven vaccine research ecosystems.</p>