Quantitative analysis of IgG class and subclass and IgA serum response to Shigella sonnei and Shigella flexneri 2a polysaccharides following vaccination with Shigella conjugate vaccines.

It has been recently reported that a conjugate vaccine composed of the O-specific polysaccharide of S. sonnei bound to Pseudomonas aeruginosa recombinant exoprotein A (rEPA) conferred 74% protection against S. sonnei shigellosis. In the present study affinity purified Shigella antibodies were used as standards to quantify and characterize the serum antibody response to vaccination with Shigella sonnei or Shigella flexneri 2a polysaccharide conjugated to rEPA. The geometric mean concentrations of antibodies at the pre-vaccination stage were 3.8 microg/ml for IgG anti-S. sonnei LPS and 11.26 microg/ml for IgG anti-S. flexneri 2a LPS. Vaccination with S. sonnei-rEPA and S. flexneri 2a-rEPA induced the production of specific IgG antibodies to levels of 115.8 microg/ml and 126.5 microg/ml, respectively. The levels of specific antibodies above the pre-vaccination values persisted for at least 2 years. The IgG response to S. flexneri 2a-rEPA conjugate was almost entirely represented by the IgG2 subclass. The concentration of IgG1 anti-S. sonnei LPS was significantly higher than that of IgG2 14 days after vaccination with the homologous conjugate, but decreased to similar levels to those of IgG2 6, 12 and 24 months after immunization. Since the only difference between the S. sonnei and S. flexneri 2a conjugates lies in the different polysaccharides of the two Shigella serogroups (the protein rEPA, is identical in both cases), it follows that the different pattern of IgG subclass response is a result of the different structures of the two O-polysaccharides of S. sonnei and S. flexneri 2a.