Procholeragenoid: A safe and effective antigen for oral immunization against experimental cholera

N. F. Pierce, W. C. Cray, J. B. Sacci, J. P. Craig, R. Germanier, E. Fürer

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1112-1118
Number of pages7
JournalInfection and Immunity
Volume40
Issue number3
StatePublished - 1983

Fingerprint

Cholera
Cholera Toxin
Immunization
Antigens
Vibrio cholerae
Poisons
Dogs
Diarrhea
Cholera Vaccines
Antitoxins
G(M1) Ganglioside
Adenylyl Cyclases
Formaldehyde
Mucous Membrane
Hot Temperature
Molecular Weight

ASJC Scopus subject areas

  • Immunology

Cite this

Pierce, N. F., Cray, W. C., Sacci, J. B., Craig, J. P., Germanier, R., & Fürer, E. (1983). Procholeragenoid: A safe and effective antigen for oral immunization against experimental cholera. Infection and Immunity, 40(3), 1112-1118.

Procholeragenoid : A safe and effective antigen for oral immunization against experimental cholera. / Pierce, N. F.; Cray, W. C.; Sacci, J. B.; Craig, J. P.; Germanier, R.; Fürer, E.

In: Infection and Immunity, Vol. 40, No. 3, 1983, p. 1112-1118.

Research output: Contribution to journalArticle

Pierce, NF, Cray, WC, Sacci, JB, Craig, JP, Germanier, R & Fürer, E 1983, 'Procholeragenoid: A safe and effective antigen for oral immunization against experimental cholera', Infection and Immunity, vol. 40, no. 3, pp. 1112-1118.
Pierce, N. F. ; Cray, W. C. ; Sacci, J. B. ; Craig, J. P. ; Germanier, R. ; Fürer, E. / Procholeragenoid : A safe and effective antigen for oral immunization against experimental cholera. In: Infection and Immunity. 1983 ; Vol. 40, No. 3. pp. 1112-1118.
@article{594e86c2681641e3b37b989a55d83aee,
title = "Procholeragenoid: A safe and effective antigen for oral immunization against experimental cholera",
abstract = "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.",
author = "Pierce, {N. F.} and Cray, {W. C.} and Sacci, {J. B.} and Craig, {J. P.} and R. Germanier and E. F{\"u}rer",
year = "1983",
language = "English (US)",
volume = "40",
pages = "1112--1118",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "3",

}

TY - JOUR

T1 - Procholeragenoid

T2 - A safe and effective antigen for oral immunization against experimental cholera

AU - Pierce, N. F.

AU - Cray, W. C.

AU - Sacci, J. B.

AU - Craig, J. P.

AU - Germanier, R.

AU - Fürer, E.

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.

UR - http://www.scopus.com/inward/record.url?scp=0020614530&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020614530&partnerID=8YFLogxK

M3 - Article

C2 - 6602094

AN - SCOPUS:0020614530

VL - 40

SP - 1112

EP - 1118

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 3

ER -