Conversion of the Yellow Fever Vaccine into an Oral Form: Scientific Feasibility, Challenges and Translational Perspectives

Abstract

Yellow fever remains a significant public health concern in endemic regions of Africa and South America despite the availability of an effective injectable vaccine. Limitations associated with parenteral administration, including cold chain dependency, need for trained personnel, and needle-related concerns, restrict widespread immunization coverage. This study explores the feasibility of developing an oral formulation of the yellow fever vaccine using modern drug delivery technologies. A narrative review and translational analysis were conducted using published literature on oral vaccines, mucosal immunity, and nanoparticle-based delivery systems. Key challenges identified include degradation of live-attenuated virus in the gastrointestinal environment, variability in immune response, and formulation stability. Emerging strategies such as enteric coating, lipid-based carriers, and polymeric nanoparticles show potential in overcoming these barriers. The findings suggest that oral vaccine delivery could significantly enhance accessibility, compliance, and population-level immunity. However, further preclinical and clinical studies are required to establish safety, efficacy, and large-scale manufacturability. The development of an oral yellow fever vaccine represents a promising direction for improving global vaccination strategies.