Abstract
Natural protection from cholera is associated with local intestinal antibacterial and antitoxic antibodies, which appear to act synergistically. Although current parenteral cholera vaccines offer insufficient protection, new vaccines administered orally have more promise. Killed Vibrio cholerae, alone or given with the B subunit of cholera toxin, was evaluated in adult volunteers. Vaccinees, who received three doses of either vaccine, and unvaccinated controls ingested 10(6) V. cholerae organisms to determine the protective efficacy of the vaccines. The combination vaccine provided 64% protection, and the whole vibrio vaccine given alone provided 56% protection. In addition, illnesses in vaccines were milder than those in controls, and both vaccines gave complete protection against more severe disease. This substantial level of protection against a dose of V. cholerae that caused cholera in nearly 90% of controls suggests that these vaccines might provide at least as high a level of protection if given to the population of an endemic area. Indeed, a field efficacy trial is underway in Bangladesh, and preliminary data indicate a protective efficacy of 85% for a killed whole vibrio plus B subunit vaccine similar to that tested in volunteers and an efficacy of 58% for the killed whole vibrio vaccine alone. Thus, the studies in human volunteers were successful in predicting the substantial protection afforded by the vaccines in a cholera endemic area.
MeSH Terms
Administration, Oral
Adolescent
Adult
Cholera/prevention & control
Cholera Toxin/administration & dosage,pharmacology
Cholera Vaccines/administration & dosage,pharmacology
Clinical Trials as Topic
Humans
Chemicals
Cholera Vaccines
Cholera Toxin
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Black R E
Levine M M
Clements M L
Young C R
Svennerholm A M
Holmgren J
References (23)
23 references, click to expand
-
Response of man to infection with Vibrio cholerae. I. Clinical, serologic, and bacteriologic responses to a known inoculum.
J Infect Dis. 1974 Jan;129(1):45-52
PMID: 4809112
-
Enzyme-linked immunosorbent assays for cholera serology.
Infect Immun. 1973 May;7(5):759-63
PMID: 4202959
-
Synergistic protective effect in rabbits of immunization with Vibrio cholerae lipopolysaccharide and toxin/toxoid.
Infect Immun. 1976 Mar;13(3):735-40
PMID: 1270131
-
Development of improved cholera vaccine based on subunit toxoid.
Nature. 1977 Oct 13;269(5629):602-4
PMID: 72361
-
The role of antigen form and function in the primary and secondary intestinal immune responses to cholera toxin and toxoid in rats.
J Exp Med. 1978 Jul 1;148(1):195-206
PMID: 670885
-
A controlled field trial of plain and aluminium hydroxide-adsorbed cholera vaccines in Surabaya, Indonesia, during 1973--75.
Bull World Health Organ. 1978;56(4):619-27
PMID: 365388
-
Selective vs. nonselective media and direct plating vs. enrichment technique in isolation of Vibrio cholerae: recommendations for clinical laboratories.
J Infect Dis. 1980 Sep;142(3):328-31
PMID: 7003031
-
Receptor-specific large-scale purification of cholera toxin on silica beads derivatized with lysoGM1 ganglioside.
Eur J Biochem. 1981 Jan;113(2):249-58
PMID: 6258916
-
Duration of infection-derived immunity to cholera.
J Infect Dis. 1981 Jun;143(6):818-20
PMID: 7252264
-
Actions of cholera toxin and the prevention and treatment of cholera.
Nature. 1981 Jul 30;292(5822):413-17
PMID: 7019725
-
Magnitude, kinetics, and duration of vibriocidal antibody responses in North Americans after ingestion of Vibrio cholerae.
J Infect Dis. 1982 Apr;145(4):465-73
PMID: 7069227
-
Oral immunization of dogs with purified cholera toxin, crude cholera toxin, or B subunit: evidence for synergistic protection by antitoxic and antibacterial mechanisms.
Infect Immun. 1982 Aug;37(2):687-94
PMID: 6889574
-
Receptor-like glycocompounds in human milk that inhibit classical and El Tor Vibrio cholerae cell adherence (hemagglutination).
Infect Immun. 1983 Jan;39(1):147-54
PMID: 6295953
-
New knowledge on pathogenesis of bacterial enteric infections as applied to vaccine development.
Microbiol Rev. 1983 Dec;47(4):510-50
PMID: 6363898
-
Evaluation of the human immune response to outer membrane proteins of Vibrio cholerae.
Infect Immun. 1984 May;44(2):439-44
PMID: 6715044
-
Mucosal antitoxic and antibacterial immunity after cholera disease and after immunization with a combined B subunit-whole cell vaccine.
J Infect Dis. 1984 Jun;149(6):884-93
PMID: 6736680
-
Enzyme-linked immunosorbent assay to measure antibodies to purified heat-labile enterotoxins from human and porcine strains of Escherichia coli and to cholera toxin: application in serodiagnosis and seroepidemiology.
J Clin Microbiol. 1985 Feb;21(2):174-9
PMID: 3882744
-
Local and systemic antibody responses and immunological memory in humans after immunization with cholera B subunit by different routes.
Bull World Health Organ. 1984;62(6):909-18
PMID: 6335849
-
Field trial of oral cholera vaccines in Bangladesh.
Lancet. 1986 Jul 19;2(8499):124-7
PMID: 2873397
-
Immunochemical quantitation of antigens by single radial immunodiffusion.
Immunochemistry. 1965 Sep;2(3):235-54
PMID: 4956917
-
The relationship of vibriocidal antibody titre to susceptibility to cholera in family contacts of cholera patients.
Bull World Health Organ. 1968;38(5):777-85
PMID: 5303331
-
Pathogenesis of experimental cholera. Preparation and isolation of choleragen and choleragenoid.
J Exp Med. 1969 Jul 1;130(1):185-202
PMID: 4978880
-
Response of man to infection with Vibrio cholerae. II. Protection from illness afforded by previous disease and vaccine.
J Infect Dis. 1974 Oct;130(4):325-33
PMID: 4443613