Artificial Salmonella vaccines: O-antigenic oligosaccharide-protein conjugates induce protection against infection with Salmonella typhimurium

Abstract

Outbred mice were vaccinated with various artificial Salmonella vaccines and subsequently challenged i.p. with graded doses of virulent S. typhimurium. The Salmonella vaccines used were octasaccharide, obtained by hydrolysis of the O-antigenic polysaccharide chain of S. typhimurium strain SH 4809 with phage P22-associated endo-rhamnosidase and covalently linked to diphtheria toxin or edestine, purified outer membrane proteins (porins) from S. typhimurium and octasaccharide covalently linked to porins. All vaccines induced significant protection against experimental infection of mice with S. typhimurium. Vaccination with the octasaccharide-porin conjugate resulted in better protection than that obtained by vaccination with octasaccharide or porin vaccines separately. Rabbit antibodies raised against the different vaccines were passively administered i.v. to mice. Such mice were protected against challenge with virulent S. typhimurium by antibodies specific for the S. typhimurium O-antigen or for the porins. Active immunization with more than 1 surface component of Salmonella bacteria improved the efficacy of the vaccine. The data from the passive immunization experiments emphasized the role of humoral immunity for protection against S. typhimurium infection.