Assay of typhoid vaccines with Salmonella typhosa-Salmonella typhimurium hybrids

Salmonella typhimurium hybrids expressing the S. typhosa antigens 9, d, and Vi were constructed by genetic crosses with an S. typhosa Hfr donor. The hybrids retained the same degree of mouse virulence as their S. typhimurium parent strain, the minimum lethal dose being less than 50 organisms when tested either in C(57) black mice or Swiss white mice. Vaccination of the Swiss white mice with S. typhosa Ty2 vaccines prepared by acetone treatment, alcohol treatment, or heat-killing conferred significant protection against challenge by the hybrid strains but not against their S. typhimurium parent. Both the acetone-treated and alcohol-treated typhoid vaccines were markedly more protective than the heat-killed, phenol-preserved vaccine.