Assessment of Typhoid Vaccines by Using the Intraperitoneal Route of Challenge

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Abstract
Present laboratory tests for human typhoid vaccines use an intraperitoneal route of challenge given 7 days after injection of increasing doses of standard and test vaccines by the same route. In studies reported here, groups of B6D2 mice were vaccinated intraperitoneally with 2 × 10 8 acetone-killed Salmonella typhi Ty2, with the Vi antigen-free variant O-901, or with Yersinia enterocolitica and Serratia marcescens suspensions. Other groups of mice received 200 μg of purified S. typhi or S. marcescens endotoxin, or their corresponding purified lipid A components. All of the vaccinated mice (except for saline- or thioglycolate-injected controls) exhibited increased protection against the lethal intraperitoneal challenge with S. typhi Ty2. Serial quantitative bacterial counts carried out on peritoneal washouts and on homogenates of the draining mediastinal lymph nodes indicated the development of an antibacterial response by the vaccinated host which was not observed in the control animals. Mice receiving purified endotoxin (lipopolysaccharide) exhibited varying degrees of protection, both in terms of increased host survival and the amount of inactivation of the challenge population in vivo. The response seen when the antigenically unrelated S. marcescens lipopolysaccharide was injected was little different from that seen when the acetone-killed S. typhi Ty2 whole-cell vaccine was used. This suggests that nonspecific inactivation of the intraperitoneal challenge contributes substantially to the immune response seen in mice vaccinated intraperitoneally with specific typhoid antigens.