Typhoid & paratyphoid vaccine development in the laboratory: a review & in-country experience.

Enteric fever is caused by the infection of Gram-negative bacteria, Salmonella enterica serovar Typhi and Salmonella enterica serovar Paratyphi (S. Paratyphi) A, B and C, through contaminated food and water. The disease almost exclusively affects the populations living in low- and middle-income countries, with the World Health Organization Southeast Asian Region (WHO SEAR) having the highest endemicity. Despite humans being the sole reservoir of infection and antibiotics and vaccines are made available, the disease was not taken up for elimination until recently due to several biological and technical reasons, including the lack of accurate and region-specific disease surveillance data in the real-time diagnostic inaccuracy of acute infections, difficulty in identifying the chronic asymptomatic carriers who are the major reservoirs of infection and the absence of a political will. However, there is now a renewed interest and effort to control the disease in the endemic areas with the help of better surveillance tools to monitor disease burden, wider availability of more accurate blood culture methods for diagnosis, and above all, cost-effective typhoid conjugate vaccines (TCVs) that can provide a high level of durable protection, particularly against the multidrug-resistant strains and to the age group most commonly affected by the disease. However, despite the commercial availability of a few TCVs, they are still in the development stage. Several questions need to be answered before they are taken up for routine immunization in countries like India. Furthermore, typhoid vaccines with a wider coverage, including additional efficacy against Salmonella Paratyphi A and B and preferably the non-typhoidal Salmonella (NTS) serovars, for which no vaccines are currently available would be more desirable. We have developed several subunit vaccine candidates containing the glycoconjugates of the surface polysaccharides of typhoidal and non-typhoidal Salmonellae and an intrinsic Salmonella protein that functions as both antigen and adjuvant. We also developed a novel mouse model of oral Salmonella Typhi infection to test the candidate vaccines, which demonstrated broad protective efficacy against Salmonella spp. through the induction of humoral and cell-mediated immunity as well as memory response.