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 intraperitoneally with graded doses of virulent Salmonella typhimurium. The Salmonella vaccines used were: (i) 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 either diphtheria toxin or edestine; (ii) purified outer membrane proteins (porins) from S. typhimurium; and (iii) octasaccharide covalently linked to porins. All vaccines induced significant protection against experimental infection of mice with S. typhimurium. However, 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 also passively administered intravenously 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. Thus, active immunization with more than one surface component of Salmonella bacteria improved the efficacy of the vaccine. The data from the passive immunization experiments also emphasized the role of humoral immunity for protection against S. typhimurium infection.

Humoral antibody responses to experimental and spontaneous Salmonella infections in cattle measured by ELISA

“…The specificity of ELISA is naturally based on the antigen preparations used. The LPS antigens used in this study have been proven to be of high purity and specificity (TORBECK et al, 1979;SVENSON et al, 1979). The possibility of measuring IgM and IgG antibodies was also verified by the use of class-specific conjugates.…”

Mechanism of the protective immunity against murine typhoid: persistence of salmonella L forms in the liver after immunization with live-cell vaccines

“…In particular, the delayed footpad response, (one measure of T cell-mediated immune responses) was completely lost one month after immunization. Contrary to the widely-accepted view of a cellular basis of salmonella immunity, an important role of antibody-dependent resistance has been implicated in salmonella immunity [12][13][14], and also octasaccharide of O antigens [15][16][17] and porins [18,19] have been identified as protective immunogens.…”

Determinants of immunity to murine salmonellosis: studies involving immunization with lipopolysaccharide-lipid A-associated protein complexes in C3H/HeJ mice

“…investigators emphasize that cell-mediated immunity elicited by viable Salmonella vaccines is responsible for the protection afforded Salmonellaimmune mice [1 3]. In contrast, other investigators have reported transfer of Salmonella immunity to naive recipients by passive transfer of immune serum [4][5][6][7][8]. Since it is now recognized, however, that a variety of distinct genetic loci can influence the relative susceptibility of mice to infection with S. typhimurium, it is probable that conclusions may well depend critically upon a number of distinct experimental factors in individual models of infection.…”