Oropouche Virus (OROV) Vaccine Development for Vulnerable Populations: Epidemiological Context, Challenges and Future Directions.

Oropouche virus (OROV) is an emerging arthropod-borne virus in the Americas that has evolved from a pathogen historically restricted to forest environments into an increasingly important regional and international public health concern. Despite decades of documented circulation, the true burden of OROV infection remains substantially underestimated, largely because of frequent misdiagnosis and the high proportion of asymptomatic or subclinical infections. This review synthesizes current evidence on the historical emergence, epidemiology, transmission dynamics, and clinical features of OROV, with a particular focus on populations at increased risk due to biological susceptibility, environmental exposure, and limited access to healthcare. Drawing on seroepidemiological data, we demonstrate that OROV transmission is far more widespread than routine surveillance suggests and examine how factors such as age, pregnancy, immune status, underlying health conditions, occupational exposure, and healthcare accessibility interact to influence disease risk and detection. Although multiple vaccine platforms have shown promise in preclinical studies, progress toward clinical development remains constrained by limited immunological evidence, shortcomings of available animal models, diagnostic uncertainty, and structural barriers in endemic regions. We propose that future OROV vaccine development prioritize population-specific needs rather than focusing solely on technological platforms, and that effective prevention will require integrating vaccination with strengthened surveillance, improved diagnostics, and equitable delivery systems.