Laura B. Martin, Raphael Simon, Calman A. MacLennan, Sharon M. Tennant, Sushant Sahastrabuddhe, M. Imran Khan
Salmonella enterica serovars Typhi and Paratyphi (S. Paratyphi) A and B cause enteric fever in humans. Of the paratyphoid group, S. Paratyphi A is the most common serovar. In 2000, there were an estimated 5.4 million cases of S. Paratyphi A worldwide. More recently paratyphoid fever has accounted for an increasing fraction of all cases of enteric fever. Although vaccines for typhoid fever have been developed and in use for decades, vaccines for paratyphoid fever have not yet been licensed. Several S. Paratyphi A vaccines, however, are development and based on either whole cell live-attenuated strains or repeating units of the lipopolysaccharide O-antigen (O:2) conjugated to different protein carriers. An O-specific polysaccharide (O:2) of S. Paratyphi A conjugated to tetanus toxoid (O:2-TT), for example, has been determined be safe and immunogenic after one dose in Phase I and Phase II trials. Two other conjugated vaccine candidates linked to diphtheria toxin and a live-attenuated oral vaccine candidate are currently in preclinical development. As promising vaccine candidates are advanced along the development pipeline, an adequate supply of vaccines will need to be generated to meet growing demand, particularly in the most affected countries.
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