A murine model of intranasal immunization to assess the immunogenicity of attenuated Salmonella typhi live vector vaccines in stimulating serum antibody responses to expressed foreign antigens

Vaccine
J E GalenM M Levine

Abstract

The lack of a practical small animal model to study the immunogenicity of Salmonella typhi-based live vector vaccines expressing foreign antigens has seriously impeded the vaccine development process. For some foreign antigens, stimulation of serum IgG antibody is the desired, protective immune response. We administered to mice, by orogastric or intranasal (i.n.) routes, attenuated delta aroC delta aroD S. typhi CVD 908 carrying a plasmid encoding fragment C (fragC) of tetanus toxin fused to the eukaryotic cell receptor binding domain of diphtheria toxin (fragC-bDt), and monitored serum antibody. While orogastric inoculation of three doses was not immunogenic, i.n. immunization elicited high titers of serum IgG tetanus antitoxin, generating peak ELISA geometric mean titers (GMT) of 27024 and 35658 with 10(8) and 10(9) c.f.u. dosages, respectively; 10(9) c.f.u. i.n. of an delta aroA S. typhimurium live vector stimulated a peak antitoxin GMT of 376 405. Mice immunized with the S. typhi live vector were 100% protected against challenge with 100 50% lethal doses of tetanus toxin that rapidly killed all control mice. Intranasal immunization with two doses of S. typhi expressing unfused fragment C under control of an anaerobically-ac...Continue Reading

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Citations

Nov 22, 2002·Trends in Biotechnology·Jos F M L Seegers
Aug 23, 2001·Advanced Drug Delivery Reviews·S S Davis
Aug 23, 2001·Advanced Drug Delivery Reviews·N MielcarekC Locht
Aug 22, 2001·Trends in Microbiology·J E Galen, M M Levine
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Sep 3, 2010·Clinical and Vaccine Immunology : CVI·Sangun LeeJohn E Herrmann
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Apr 12, 2002·The Lancet Infectious Diseases·John WainGordon Dougan
Oct 28, 1998·Molecular Aspects of Medicine·G Del GiudiceR Rappuoli
Sep 4, 1999·Lancet·A SinhaM K Bhan
Sep 4, 1999·Lancet·G E Griffin

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