Single-dose Live Oral Cholera Vaccine CVD 103-HgR Protects Against Human Experimental Infection With Vibrio Cholerae O1 El Tor

Clin Infect Dis. 2016 Jun 1;62(11):1329-1335. doi: 10.1093/cid/ciw145. Epub 2016 Mar 21.

Abstract

Background: No licensed cholera vaccine is presently available in the United States. Cholera vaccines available in other countries require 2 spaced doses. A single-dose cholera vaccine that can rapidly protect short-notice travelers to high-risk areas and help control explosive outbreaks where logistics render 2-dose immunization regimens impractical would be a major advance.PXVX0200, based on live attenuated Vibrio cholerae O1 classical Inaba vaccine strain CVD 103-HgR, elicits seroconversion of vibriocidal antibodies (a correlate of protection) within 10 days of a single oral dose. We investigated the protection conferred by this vaccine in a human cholera challenge model.

Methods: Consenting healthy adult volunteers, 18-45 years old, were randomly allocated 1:1 to receive 1 oral dose of vaccine (approximately 5 × 10(8) colony-forming units [CFU]) or placebo in double-blind fashion. Volunteers ingested approximately 1 × 10(5) CFU of wild-type V. cholerae O1 El Tor Inaba strain N16961 10 days or 3 months after vaccination and were observed on an inpatient research ward for stool output measurement and management of hydration.

Results: The vaccine was well tolerated, with no difference in adverse event frequency among 95 vaccinees vs 102 placebo recipients. The primary endpoint, moderate (≥3.0 L) to severe (≥5.0 L) diarrheal purge, occurred in 39 of 66 (59.1%) placebo controls but only 2 of 35 (5.7%) vaccinees at 10 days (vaccine efficacy, 90.3%; P < .0001) and 4 of 33 (12.1%) vaccinees at 3 months (vaccine efficacy, 79.5%; P < .0001).

Conclusions: The significant vaccine efficacy documented 10 days and 3 months after 1 oral dose of PXVX0200 supports further development as a single-dose cholera vaccine.

Clinical trials registration: NCT01895855.

Keywords: challenge; cholera; efficacy; vaccine; volunteer.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Bacterial / blood*
  • Antibodies, Bacterial / immunology
  • Cholera / immunology
  • Cholera / prevention & control*
  • Cholera Vaccines / administration & dosage*
  • Cholera Vaccines / adverse effects
  • Cholera Vaccines / immunology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Vibrio cholerae O1 / immunology*
  • Young Adult

Substances

  • Antibodies, Bacterial
  • Cholera Vaccines
  • cholera vaccine CVD 103-HgR

Associated data

  • ClinicalTrials.gov/NCT01895855