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Role of monoclonal O-antigen antibody epitope specificity and isotype in protection against experimental mouse
N I Carlin1, S B Svenson, A A Lindberg
1Department of Vaccine Production, National Bacteriological Laboratory, Stockholm, Sweden.
Abstract:
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.
Insights
Researchers developed monoclonal antibodies targeting Salmonella typhimurium. Antibody isotype and epitope specificity significantly influence protective immunity against typhoid fever in mice.
Area of Science:
- Immunology
- Microbiology
- Bacteriology
Background:
- Lipopolysaccharide (LPS) O-antigenic polysaccharide chains are crucial components of the Salmonella typhimurium cell envelope.
- Understanding antibody interactions with LPS is vital for developing effective typhoid fever treatments and vaccines.
Purpose of the Study:
- To establish and characterize monoclonal antibodies specific to the O-antigenic polysaccharide of Salmonella typhimurium.
- To evaluate the protective efficacy of these monoclonal antibodies in a mouse model of typhoid fever.
Main Methods:
- Development of 14 monoclonal antibodies against Salmonella typhimurium O-antigen.
- Specificity determination using passive hemagglutination and enzyme immunoassays with various Salmonella saccharide antigens.
- Assessment of passive protection in a mouse model challenged with Salmonella typhimurium SH2201.
Main Results:
- Monoclonal antibodies were classified into five epitope specificity groups: O4, O4,12, O4,12(2), O5, and O12.
- IgG3 monoclonal antibodies showed protective activity in the order O4 > O4,12 > O4,12(2) >= O12, with a >2500-fold difference between O4 and O12.
- IgM antibodies (O4,12 and O12 specific) were highly protective, while IgA antibodies (O5 specific) were not protective.
Conclusions:
- Both antibody isotype and epitope specificity are critical factors in determining the protective capacity against Salmonella typhimurium infection.
- The findings highlight the potential of specific monoclonal antibodies for therapeutic intervention in typhoid fever.