Safety, Immunogenicity and Dose Ranging of a New Vi-CRM.sub.197 Conjugate Vaccine against Typhoid Fever: Randomized Clinical Testing in Healthy Adults

Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM.sub.197) for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM.sub.197 in European adults. Following randomized blinded comparison of single vaccination with either Vi-CRM.sub.197 or licensed polysaccharide vaccines (both containing 25·0 [micro]g of Vi antigen), a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM.sub.197 (1·25 [micro]g, 5·0 [micro]g and 12·5 [micro]g of Vi antigen) with the polysaccharide vaccine. Vi-CRM.sub.197 did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia.