TY - JOUR
T1 - Procholeragenoid
T2 - A safe and effective antigen for oral immunization against experimental cholera
AU - Pierce, Nathaniel F.
AU - Cray, William C.
AU - Sacci, John B.
AU - Craig, John P.
AU - Germanier, René
AU - Fürer, Emil
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1983
Y1 - 1983
N2 - The immunogenicity and safety of procholeragenoid, a minimally toxic, heat-induced aggregate of cholera toxin (CT), were studied in enterically immunized rats and dogs. Although 99% less toxic than CT, procholeragenoid was only slightly less efficient in causing jejunal anti-CT responses in rats; in contrast choleragenoid, the nontoxic B subunit pentamer of CT, was much less effective. The immunogenicity of procholeragenoid was due almost entirely to its large-molecular-weight components (MW = 106 to 107) and was markedly reduced by preincubation with GM1 ganglioside or treatment with Formalin to eliminate residual toxicity. These findings suggest that molecular aggregation, binding to GM1 receptors on cell membranes, and stimulation of cellular adenylate cyclase each contributed to the effectiveness of procholeragenoid as a mucosal immunogen. In dogs, oral immunization with five 500-mg doses of procholeragenoid evoked vigorous anti-CT responses in jejunal mucosa without causing significant diarrhea. When subsequently challenged with virulent vibrio cholerae, immunized dogs showed 83% protection against the development of severe or lethal diarrhea compared with non-immunized controls. These results confirm a protective role for mucosal antitoxin in experimental cholera and show that procholeragenoid is both safe and effective as an oral immunogen. Procholeragenoid, combined with other antigens of V. cholerae, may constitute a simple, safe, and effective oral vaccine for cholera.
AB - The immunogenicity and safety of procholeragenoid, a minimally toxic, heat-induced aggregate of cholera toxin (CT), were studied in enterically immunized rats and dogs. Although 99% less toxic than CT, procholeragenoid was only slightly less efficient in causing jejunal anti-CT responses in rats; in contrast choleragenoid, the nontoxic B subunit pentamer of CT, was much less effective. The immunogenicity of procholeragenoid was due almost entirely to its large-molecular-weight components (MW = 106 to 107) and was markedly reduced by preincubation with GM1 ganglioside or treatment with Formalin to eliminate residual toxicity. These findings suggest that molecular aggregation, binding to GM1 receptors on cell membranes, and stimulation of cellular adenylate cyclase each contributed to the effectiveness of procholeragenoid as a mucosal immunogen. In dogs, oral immunization with five 500-mg doses of procholeragenoid evoked vigorous anti-CT responses in jejunal mucosa without causing significant diarrhea. When subsequently challenged with virulent vibrio cholerae, immunized dogs showed 83% protection against the development of severe or lethal diarrhea compared with non-immunized controls. These results confirm a protective role for mucosal antitoxin in experimental cholera and show that procholeragenoid is both safe and effective as an oral immunogen. Procholeragenoid, combined with other antigens of V. cholerae, may constitute a simple, safe, and effective oral vaccine for cholera.
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U2 - 10.1128/iai.40.3.1112-1118.1983
DO - 10.1128/iai.40.3.1112-1118.1983
M3 - Article
C2 - 6602094
AN - SCOPUS:0020614530
SN - 0309-1708
VL - 40
SP - 1112
EP - 1118
JO - Unknown Journal
JF - Unknown Journal
IS - 3
ER -