Safety, immunogenicity and preliminary protective efficacy of a bivalent bacterial ghost vaccine against typhoidal Salmonella in rabbits: a pilot study

The global health burden from enteric fever, caused by Salmonella enterica serovars Typhi and Paratyphi A, is exacerbated by the emergence of drug resistance. This growing resistance undermines the effectiveness of empirical antibiotic treatments and narrows the options for definitive antimicrobial therapy. Presence of vaccines against typhoidal strains has caused an evolutionary selection of paratyphoid strains, causing rising incidence of paratyphoid fever, particularly in the Southeast Asian countries. This calls for a bivalent vaccine against both the serotypes to provide a broad-spectrum prophylactic protection. The present study describes the design of a cost-effective, bivalent immunogen based on bacterial ghost technology, targeting S. Typhi and S. Paratyphi A. Its preliminary protective efficacy was subsequently evaluated using a rabbit oral infection and bacterial shedding model. The bivalent immunogen was found to be eliciting robust, antigen-specific immunity against both serovars without any reactogenicity. These findings provide useful pre-clinical results paving the way for a future bacterial ghost-based vaccine as a safe, cost effective and promising candidate strategy to prevent enteric fever.