Clinical Infectious Diseases
2016 Mar 21. pii: ciw145. [Epub ahead of print]
Single-Dose Live Oral Cholera Vaccine CVD 103-HgR Protects Against Human Experimental Infection with Vibrio cholerae O1 El Tor.
WH Chen, MB Cohen, BD Kirkpatrick, RC Brady… –
Abstract
BACKGROUND:
No licensed cholera vaccine is presently available in the U.S.A. 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 two-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 one oral dose of vaccine (∼5×108 colony forming units, CFU) or placebo in double-blind fashion. Volunteers ingested ∼1×105 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 versus 102 placebo recipients. The primary endpoint, moderate (≥3.0 liter) to severe (≥5.0 liter) diarrheal purge occurred in 39/66 (59.1%) placebo controls but only 2/35 (5.7%) vaccinees at 10 days (vaccine efficacy=90.3%, p<0.0001) and 4/33 (12.1%) vaccinees at 3 months (vaccine efficacy=79.5%, p<0.0001).
CONCLUSIONS:
The significant vaccine efficacy documented 10 days and 3 months after one oral dose of PXVX0200 supports further development as a single-dose cholera vaccine.