Abstract
This report describes studies of the mucosal antitoxic response in rats after enteric administration of several forms of cholera toxin or toxoid, proteins which differ primarily in their ability to bind to cell membranes and activate cellular adenyl cyclase. These two characteristics appeared to markedly enhance the local primary response to these antigens. A single dose of toxoid lacking these features was ineffective in local priming even though it was absorbed and induced a systemic immune response. Single dose mucosal priming occurred only with preparations which bind to cell membranes and was enhanced by those which also activate cellular adenyl cyclase. In contrast, single-dose mucosal boosting was best accomplished by materials with these properties but was also seen with a toxoid lacking both of these functions. The property of membrane binding appears to be most advantageous in mucosal priming, perhaps by increasing effective trapping of absorbed antigen in unprimed mucosal lymphoid tissue, whereas the ability to activate adenyl cyclase appears to enhance primary and secondary type responses about equally. Combinations of crude toxoid and toxin were also more effective in mucosal priming than purified materials, a finding which is unexplained. A single dose of this combination induced mucosal priming which was fully developed in 2 wk, undiminished after 4 too, and only modestly diminished after 8 mo, thus demonstrating relatively prolonged memory in the IgA mucosal immune system. Effective two-dose local immunizing regimens were developed, and it was shown that there was no correlation between the mucosal and systemic secondary antitoxin responses provoked by these regimens.
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Selected References
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- Brandtzaeg P. Mucosal and glandular distribution of immunoglobulin components. Immunohistochemistry with a cold ethanol-fixation technique. Immunology. 1974 Jun;26(6):1101–1114. [PMC free article] [PubMed] [Google Scholar]
- Crabbé P. A., Nash D. R., Bazin H., Eyssen D. V., Heremans J. F. Antibodies of the IgA type in intestinal plasma cells of germfree mice after oral or parenteral immunization with ferritin. J Exp Med. 1969 Oct 1;130(4):723–744. doi: 10.1084/jem.130.4.723. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Craig J. P. Preparation of the vascular permeability factor of Vibrio cholerae. J Bacteriol. 1966 Sep;92(3):793–795. doi: 10.1128/jb.92.3.793-795.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cuatrecasas P. Vibrio cholerae choleragenoid. Mechanism of inhibition of cholera toxin action. Biochemistry. 1973 Aug 28;12(18):3577–3581. doi: 10.1021/bi00742a034. [DOI] [PubMed] [Google Scholar]
- Finkelstein R. A., LoSpalluto J. J. Pathogenesis of experimental cholera. Preparation and isolation of choleragen and choleragenoid. J Exp Med. 1969 Jul 1;130(1):185–202. doi: 10.1084/jem.130.1.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Finkelstein R. A. Monospecific equine antiserum against cholera exo-enterotoxin. Infect Immun. 1970 Dec;2(6):691–697. doi: 10.1128/iai.2.6.691-697.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Flores J., Witkum P., Sharp G. W. Activation of adenylate cyclase by cholera toxin in rat liver homogenates. J Clin Invest. 1976 Feb;57(2):450–458. doi: 10.1172/JCI108296. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holmgren J., Lindholm L. Cholera toxin, ganglioside receptors and the immune response. Immunol Commun. 1976;5(9):737–756. doi: 10.3109/08820137609047617. [DOI] [PubMed] [Google Scholar]
- Ishizuka M., Braun W., Matsumoto T. Cyclic AMP and immune responses. I. Influence of poly A:U and cAMP on antibody formation in vitro. J Immunol. 1971 Oct;107(4):1027–1035. [PubMed] [Google Scholar]
- Kagnoff M. F., Campbell S. Functional characteristics of Peyer's patch lymphoid cells. I. Induction of humoral antibody and cell-mediated allograft reactions. J Exp Med. 1974 Feb 1;139(2):398–406. doi: 10.1084/jem.139.2.398. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kimberg D. V., Field M., Johnson J., Henderson A., Gershon E. Stimulation of intestinal mucosal adenyl cyclase by cholera enterotoxin and prostaglandins. J Clin Invest. 1971 Jun;50(6):1218–1230. doi: 10.1172/JCI106599. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mozes E., Weinstein Y., Bourne H. R., Melmon K. L., Shearer G. M. In vitro correction of antigen-induced immune suppression: effects of histamine, dibutyryl cyclic AMP and cholera enterotoxin. Cell Immunol. 1974 Mar 30;11(1-3):57–63. doi: 10.1016/0008-8749(74)90006-9. [DOI] [PubMed] [Google Scholar]
- Northrup R. S., Fauci A. S. Adjuvant effect of cholera enterotoxin on the immune response of the mouse to sheep red blood cells. J Infect Dis. 1972 Jun;125(6):672–673. doi: 10.1093/infdis/125.6.672. [DOI] [PubMed] [Google Scholar]
- Pierce N. F., Gowans J. L. Cellular kinetics of the intestinal immune response to cholera toxoid in rats. J Exp Med. 1975 Dec 1;142(6):1550–1563. doi: 10.1084/jem.142.6.1550. [DOI] [PMC free article] [PubMed] [Google Scholar]