title: Randomized, controlled human challenge study of the safety, immunogenicity, and protective efficacy of a single dose of Peru-15, a live attenuated oral cholera vaccine.
abstract: Peru-15 is a live attenuated oral vaccine derived from a Vibrio cholerae O1 El Tor Inaba strain by a series of deletions and modifications, including deletion of the entire CT genetic element. Peru-15 is also a stable, motility-defective strain and is unable to recombine with homologous DNA. We wished to determine whether a single oral dose of Peru-15 was safe and immunogenic and whether it would provide significant protection against moderate and severe diarrhea in a randomized, double-blind, placebo-controlled human volunteer cholera challenge model. A total of 59 volunteers were randomly allocated to groups to receive either 2 x 10(8) CFU of reconstituted, lyophilized Peru-15 vaccine diluted in CeraVacx buffer or placebo (CeraVacx buffer alone). Approximately 3 months after vaccination, 36 of these volunteers were challenged with approximately 10(5) CFU of virulent V. cholerae O1 El Tor Inaba strain N16961, prepared from a standardized frozen inoculum. Among vaccinees, 98% showed at least a fourfold increase in vibriocidal antibody titers. After challenge, 5 (42%) of the 12 placebo recipients and none (0%) of the 24 vaccinees had moderate or severe diarrhea (> or = 3,000 g of diarrheal stool) (P = 0.002; protective efficacy, 100%; lower one-sided 95% confidence limit, 75%). A total of 7 (58%) of the 12 placebo recipients and 1 (4%) of the 24 vaccinees had any diarrhea (P < 0.001; protective efficacy, 93%; lower one-sided 95% confidence limit, 62%). The total number of diarrheal stools, weight of diarrheal stools, incidence of fever, and peak stool V. cholerae excretion among vaccinees were all significantly lower than in placebo recipients. Peru-15 is a well-tolerated and immunogenic oral cholera vaccine that affords protective efficacy against life-threatening cholera diarrhea in a human volunteer challenge model. This vaccine may therefore be a safe and effective tool to prevent cholera in travelers and is a strong candidate for further evaluation to prevent cholera in an area where cholera is endemic.
authors.affiliation: Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. mitchell.cohen@chmcc.org
authors.forename: Mitchell B
authors.initials: MB
authors.lastname: Cohen
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Giannella
authors.forename: Judy
authors.initials: J
authors.lastname: Bean
authors.forename: David N
authors.initials: DN
authors.lastname: Taylor
authors.forename: Susan
authors.initials: S
authors.lastname: Parker
authors.forename: Amy
authors.initials: A
authors.lastname: Hoeper
authors.forename: Stephen
authors.initials: S
authors.lastname: Wowk
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hawkins
authors.forename: Sims K
authors.initials: SK
authors.lastname: Kochi
authors.forename: Gilbert
authors.initials: G
authors.lastname: Schiff
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Killeen
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D022121:Cholera Vaccines / Q000009:adverse effects / Q000276:immunology*; D004311:Double-Blind Method; D006801:Humans; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D022121:Cholera Vaccines; D014613:Vaccines, Attenuated