Vi capsular polysaccharide-protein conjugates for prevention of typhoid fever

Enteric fevers continue to cause considerable morbidity and mortality in nations that have not yet achieved control of drinking water and sewage disposal (1, 2). In these countries, the most frequent and serious cause of enteric fevers is Salmonella typhi (typhoid fever) (2). Immunoprophylaxis against typhoid fever on a world-wide basis has not been attempted because the two available vaccines have limitations; (a) cellular typhoid vaccines induce only a limited immunity and elicit side reactions that are frequent and severe enough to have discouraged their widespread acceptance (2, 3) ; and (b) an orally administered attenuated strain of S. typhi, Ty-21a, requires three to four doses to induce about 65% protection, it is expensive, and its mode of protection has not been identified, which has prevented precise standardization of the vaccine (1, 4). Recently, two clinical evaluations in populations with high rates of typhoid fever (-..1 %/annum) have provided evidence that immunization with the capsular polysaccharide (CPS) ' of S. typhi (Vi) confers immunity against typhoid fever (5, 6). The Vi vaccine, prepared under conditions that did not change its structure