Role of monoclonal O-antigen antibody epitope specificity and isotype in protection against experimental mouse typhoid.

A panel of 14 monoclonal antibodies with specificity for the O-antigenic polysaccharide chain of the lipopolysaccharide of the cell envelope of Salmonella typhimurium was established. The specificity of each antibody clone was determined against a set of Salmonella saccharide antigens, natural and synthetic, in passive hemagglutination and enzyme immunoassays. The monoclonal antibodies could be classified into at least five different groups: (i) O4 epitope specific, (ii) O4,12 specific, (iii) O4,12(2) specific, (iv) O5 specific, and (v) O12 specific. These specificities correspond to different structural and conformational domains of the polysaccharide chain, and often extend over more than one repeating unit (tetrasaccharide) of the polymer. The passive protection afforded by these antibodies was estimated in an experimental mouse typhoid model using S. typhimurium SH2201 for intraperitoneal challenge. Monoclonal antibodies of the IgG3 isotype were available for four of the epitope groups and were protective in the following order of activity O4 greater than O4,12 greater than O4,12(2) greater than or equal to O12. The difference between O4 and 012 antibodies was greater than 2500 fold in protective activity. Antibodies of the IgM class were highly protective irrespective of being of the O4,12 or O12 epitope specificity. Two IgA antibodies with O5 epitope specificity were not protective. The results show that both isotype and epitope specificity can be of importance for the protective ability of antibodies generated by the host.