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

Abstract

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.

Effect of parenteral immunization on the local immunoglobulin A response of the intestine to Shigella flexneri antigens

“…In the present study, we make use of our wellcharacterized, chronically isolated, ileal loop model in rabbits to follow the kinetics of the local immune response to parenterally administered Shigella flexneri antigen (8,10,11). Our earlier studies with this model system have demonstrated that a vigorous secretory IgA memory response can be elicited in intestinal secretions by oral priming with live, locally…”

“…invasive Shigella X16 (a hybrid of Escherichia coli and S. flexneri) (7)(8)(9)(10)(11)(12)(13). The present study demonstrates that local IgA response can be elicited to S. flexneri by parenterally administered, killed Shigella X16.…”

“…The doses of Shigella X16 and the routes used to immunize the animals are outlined in Table 1. The combined subcutaneous and intravenous dosage to achieve a vigorous systemic immune response was from a previously described regimen (8,11).…”

Rabbit model for mucosal immunity in the bowel: I. establishment of virus‐infected ileal loops

“…Originally employed in investigations of intestinal absorption [Parsons, 19671, Thiry-VelIa loops have recently been used in a number of studies of secretory IgA immune responses occurring in the bowel of rabbits , 1981, 1982. Few, however, have considered variables inherent in the loop model itself that might affect the results obtained.…”

“…The problem of the accessibility of tissues for inoculation and sampling was overcome by adapting the chronically isolated Thiry -Vella rabbit ileal loop model of Keren et al [ 19751. This model has been extensively employed in investigations of local IgA responses to various antigens including bacteria , 1981, 1982 and keyhole limpet hemocyanin [Hamilton et al, 19781. It was necessary to find a virus which would not normally infect this site, but which was capable of replicating and persisting locally in the isolated loops, in order to avoid the likelihood of experimental results being obscured by anamnestic responses. Paramyxoviruses, although normally respiratory pathogens, are known to be capable of replicating in small intestinal organ cultures [Rubenstein and Tyrreli, 19701 and have been shown to infect other nonrespiratory tissues, including lymphoid cells, neurones, and the endothelial cells of blood vessels and the urinary bladder [Russell and Edington, 19851.…”