Evaluation of two Salmonella typhimurium hybrids as challenge organisms in a system for the assay of typhoid vaccines.

A mouse-virulent Salmonella typhimurium hybrid (H42), which expresses the Salmonella typhi Vi antigen in addition to S. typhi O antigens 9 and 12, and a mouse-virulent S. typhimurium hybrid (H1), which expresses only the 9 and 12 antigens of S. typhi, were compared in their behavior as challenge organisms in a system developed to assay the protective capabilities of typhoid vaccines. Swiss-Webster white mice, vaccinated intraperitoneally with live Escherichia coli hybrids expressing the S. typhi O antigens 9 and 12, were significantly protected against death from intraperitoneal challenge with each of the S. typhimurium hybrid strains. Vaccination with an E. coli hybrid expressing the S. typhi Vi antigen in addition to O antigens 9 and 12 was seen to confer no advantage in protection against either S. typhimurium hybrid challenge organism over that obtained by vaccination with an E. coli hybrid expressing only the O antigens of S. typhi. However, a notable difference in the behavior of the two S. typhimurium hybrids was seen in mice vaccinated with the parent of the E. coli hybrid vaccinating strains, E. coli F464, which expresses no surface antigens common to either of these S. typhimurium hybrid challenge organisms. A nonspecific (with respect to the vaccinating strain) protective effect, believed to be associated with Vi antigen expression by the challenge organism, was seen against the challenge with S. typhimurium hybrid H42 after F464 vaccination, whereas no protection was conferred by F464 vaccination against the challenge with Vi-nonexpressing S. typhimurium hybrid H1. Inasmuch as neither S. typhimurium hybrid discriminates between the expression or nonexpression of the Vi antigen in a vaccinating strain, it is concluded that the Vi-nonexpressing S. typhimurium hybrid H1, which more clearly indicates the vaccine-specific protective role of the S. typhi O antigens and does not exhibit the nonspecific protection response of hybrid H42, is the better choice as challenge organism for this vaccine assay system.