A synthetic carbohydrate-protein conjugate vaccine candidate against Shigella flexneri 2a infection.

Abstract

The protective Ag of Shigella, the Gram-negative enteroinvasive bacterium causing bacillary dysentery, or shigellosis, is its O-specific polysaccharide (O-SP) domain of the LPS, the major bacterial surface component. As an alternative to the development of detoxified LPS-based conjugate vaccines, recent effort was put into the investigation of neoglycoproteins encompassing synthetic oligosaccharides mimicking the protective Ags of the O-SP. We previously reported that when coupled to tetanus toxoid via single point attachment, a synthetic pentadecasaccharide representing three biological repeating units of the O-SP of Shigella flexneri 2a (SF2a), one of the most common Shigella serotypes, elicits a better serum anti-LPS 2a Ab response in mice than shorter synthetic O-SP sequences. In this study, we show that the pentadecasaccharide-induced anti-LPS 2a Abs protect passively administered naive mice from Shigella infection. Therefore, this three repeating units sequence, which is recognized by anti-SF2a sera from infected patients, acts as a functional mimic of the native polysaccharide Ag. Analyses of parameters influencing immunogenicity revealed that an investigational SF2a vaccine displaying a pentadecasaccharide:tetanus toxoid molar loading of 14:1 triggers a high and sustained anti-LPS Ab response, without inducing anti-linker Ab, when administered four times at a dose corresponding to 1 mug of carbohydrate. In addition, the profile of the anti-LPS Ab response, dominated by IgG1 production (Th2-type response), mimics that observed in human upon natural SF2a infection. This synthetic carbohydrate-based conjugate may be a candidate for a SF2a vaccine.

• Authors: Armelle Phalipon, Myriam Tanguy, Cyrille Grandjean, Catherine Guerreiro, Frédéric Bélot, Dani Cohen, Philippe J Sansonetti, Laurence A Mulard
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 182 Issue 4 Pg. 2241-7 (Feb 15 2009) ISSN: 1550-6606 [Electronic] United States
• PMID: 19201878 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Bacterial
• Antigens, Bacterial
• Bacterial Vaccines
• Lipopolysaccharides
• O Antigens
• Vaccines, Conjugate

Topics

• Animals
• Antibodies, Bacterial (immunology)
• Antigens, Bacterial (immunology)
• Bacterial Vaccines (immunology)
• Dysentery, Bacillary (immunology, prevention & control)
• Enzyme-Linked Immunosorbent Assay
• Humans
• Lipopolysaccharides (immunology)
• Mice
• Mice, Inbred BALB C
• O Antigens (immunology)
• Shigella flexneri (immunology)
• Vaccines, Conjugate (immunology)