Protection against mouse typhoid by artificial Salmonella vaccines

Abstract

Salmonella serogroup BO antigen specific octasaccharides were isolated from phage P22 endo-rhamnosidase cleaved S. typhimurium O-polysaccharide chains. The O-antigen 4, 12 specific octasaccharide, covalently linked to different carrier proteins, elicited both in rabbits and mice antibodies with specificity for the S. typhimurium O-antigens. Mice vaccinated with these octasaccharide-conjugates were protected against challenge infections with O-antigenic homologous Salmonella. The importance of humoral immunity directed against the O-antigen determinants was evidenced by the protective capacity of passively transferred antioctasaccharide antibodies and also of antibodies elicited by an O-antigen 4 specific 3-O-alpha-abequopyranosyl-alpha-D-mannopyranoside-bovine serum albumin conjugate. Also a purified outer membrane protein preparation mediated, in vaccinated mice, protection against challenge infection with S. typhimurium. Coupling of the octasaccharide to the outer membrane proteins resulted in a vaccine which protected mice against a double as high challenge dose than could either of the two components. In conclusion, the use of O-antigenic oligosaccharides covalently attached to outer membrane protein preparations raises the possibility of producing defined and atoxic vaccines against enterobacterial infections.