SIV-Salmonella Constructs and their Potential as Vaccine Candidates
Live attenuated salmonellae are effective as carriers of antigens from other pathogens (combined live oral vaccines) and can elicit humoral, secretory and cellular immunity to the recombinant antigens. We have described a new class of live attenuated Salmonella vaccines harbouring lesions in htrA, a stress protein gene (Chatfield et al., 1992). These Salmonella htrA mutants are of reduced virulence when administered either orally or intravenously, and they are effective as live oral vaccines, conferring significant protection against oral challenge in BALB/c mice. The virulence and invasiveness of Salmonella htrA mutants was investigated in three models of increased susceptibility to salmonella infection. These included BALB/c mice, either given sublethal whole body irradiation (350 R) or administered rabbit anti-TNFα antiserum, and (CBA/N x BALB/C)F1 male mice which express the xid sex linked B cell defect of CBA/N mice and are more susceptible to salmonellae than female littermates. S. typhimurium htra mutants derived from virulent strains, C5046 (C5 htrA::TnphoA) and BRD726 (SL1344 AhtrA) were not more invasive in immunosuppressed mice than in normal controls in the three mouse models of defective immunity. These results indicate that susceptibility to S. typhimunum htrA vaccines is not enhanced by conditions of impaired resistance to infection.
KeywordsToxicity Doyle Cholera Lyase Erwinia
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