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
| Autor: | Gilbert M. Schiff, Stephen Wowk, Ralph A. Giannella, Susan Parker, Kevin P. Killeen, Mitchell B. Cohen, Sims K. Kochi, Judy Bean, David N. Taylor, Jennifer Hawkins, Amy Hoeper |
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| Rok vydání: | 2002 |
| Předmět: |
Adult
Adolescent Immunology Vaccines Attenuated medicine.disease_cause Microbiology El Tor Double-Blind Method Vibrionaceae medicine Humans biology business.industry Vaccination Antibody titer Cholera Vaccines medicine.disease biology.organism_classification Antibodies Bacterial Cholera Diarrhea Infectious Diseases Vibrio cholerae Microbial Immunity and Vaccines Parasitology medicine.symptom Cholera vaccine business |
| Zdroj: | Infection and Immunity. 70:1965-1970 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.70.4.1965-1970.2002 |
| Popis: | 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 × 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 (≥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. |
| Databáze: | OpenAIRE |
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