Abstract
BACKGROUND: Enteric disease caused by Shigella, Campylobacter, and enterotoxigenic Escherichia coli (ETEC) represents a significant global health burden, particularly among children in low-resource settings. However, no licensed vaccines are currently available for these bacterial pathogens. Given the wide range of enteric pathogens and the constraints posed by an increasingly crowded infant immunization schedule, the development of combination vaccines or combined administration of individual oral vaccines may offer a practical approach to address this unmet need. OBJECTIVES: In this study, we evaluated the combined administration of two multicomponent oral vaccine candidates: ETVAX, targeting ETEC, and a trivalent whole-cell vaccine targeting Shigella. METHODS: The vaccine candidates were administered orally in mice, both individually and in combination, with and without the inclusion of the double-mutant heat-labile toxin (dmLT) adjuvant. RESULTS: The results demonstrated systemic and intestinal-mucosal immune responses to the key protective antigens following both individual and combined vaccine administration. Importantly, the combination of the two vaccines did not compromise the elicitation of specific antibody responses. The inclusion of dmLT as an adjuvant significantly enhanced immune responses to several antigens, highlighting its potential to improve vaccine efficacy. CONCLUSIONS: These findings underscore the feasibility of combining ETEC and Shigella vaccine candidates into a single formulation without compromising immunogenicity. This combined approach has the potential to provide broad protective coverage, thereby mitigating the global impact of enteric diseases and streamlining vaccine delivery within existing childhood immunization programs. Our results support further development of this combination vaccine strategy as a promising tool in combating enteric infections and improving health outcomes, particularly among young children in endemic regions who are vulnerable to enteric disease.