Role of antigen form in development of mucosal immunoglobin A response to Shigella flexneri Antigens

One major stumbling block in the development of an effective means to immunize against shigellosis and other enteric diseases has been the lack of a means to assess sequential mucosal immune responses to different potential immunogens. In the present study, we compared the abilities of live invasive organisms, noninvasive organisms, and nonviable antigen preparations of shigella to elicit mucosal immune responses. Whereas previous studies have found that effective immunity was produced best by vaccination with live invasive strains of shigella, in the present study, live noninvasive strains that did not produce any histopathological damage were consistently able to produce local (immunoglobulin A) immune responses as vigorous as those of the invasive strains. Further, acetone-killed shigella antigen was also an effective mucosal immunogen, whereas hot phenol-water-extracted shigella lipopolysaccharide was ineffective, possibly due to the method of preparation. A single oral or parenteral priming was ineffective in enhancing the mucosal immune response when restimulated 1 month later with the same antigen. However, a mucosal memory response was found to be present several months after a triple mucosal stimulation with a locally invasive vaccine strain.