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Single-dose Live Oral Cholera Vaccine CVD 103-HgR Protects Against Human Experimental Infection With Vibrio cholerae O1 El Tor.
Clin Infect Dis. 2016 06 01; 62(11):1329-1335.CI

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.

Authors+Show Affiliations

Center for Vaccine Development, University of Maryland School of Medicine, Baltimore.Cincinnati Children's Hospital Medical Center, Ohio.Vaccine Testing Center, University of Vermont College of Medicine, Burlington.Cincinnati Children's Hospital Medical Center, Ohio.Cincinnati Children's Hospital Medical Center, Ohio.PaxVax, Inc, Menlo Park, California.National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.Center for Vaccine Development, University of Maryland School of Medicine, Baltimore.PaxVax, Inc, Menlo Park, California.PaxVax, Inc, Menlo Park, California.Vaccine Testing Center, University of Vermont College of Medicine, Burlington.Center for Vaccine Development, University of Maryland School of Medicine, Baltimore.PaxVax, Inc, Menlo Park, California.Cincinnati Children's Hospital Medical Center, Ohio.Center for Vaccine Development, University of Maryland School of Medicine, Baltimore.Center for Vaccine Development, University of Maryland School of Medicine, Baltimore.

Pub Type(s)

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

Language

eng

PubMed ID

27001804

Citation

Chen, Wilbur H., et al. "Single-dose Live Oral Cholera Vaccine CVD 103-HgR Protects Against Human Experimental Infection With Vibrio Cholerae O1 El Tor." Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, vol. 62, no. 11, 2016, pp. 1329-1335.
Chen WH, Cohen MB, Kirkpatrick BD, et al. Single-dose Live Oral Cholera Vaccine CVD 103-HgR Protects Against Human Experimental Infection With Vibrio cholerae O1 El Tor. Clin Infect Dis. 2016;62(11):1329-1335.
Chen, W. H., Cohen, M. B., Kirkpatrick, B. D., Brady, R. C., Galloway, D., Gurwith, M., Hall, R. H., Kessler, R. A., Lock, M., Haney, D., Lyon, C. E., Pasetti, M. F., Simon, J. K., Szabo, F., Tennant, S., & Levine, M. M. (2016). Single-dose Live Oral Cholera Vaccine CVD 103-HgR Protects Against Human Experimental Infection With Vibrio cholerae O1 El Tor. Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, 62(11), 1329-1335. https://doi.org/10.1093/cid/ciw145
Chen WH, et al. Single-dose Live Oral Cholera Vaccine CVD 103-HgR Protects Against Human Experimental Infection With Vibrio Cholerae O1 El Tor. Clin Infect Dis. 2016 06 1;62(11):1329-1335. PubMed PMID: 27001804.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Single-dose Live Oral Cholera Vaccine CVD 103-HgR Protects Against Human Experimental Infection With Vibrio cholerae O1 El Tor. AU - Chen,Wilbur H, AU - Cohen,Mitchell B, AU - Kirkpatrick,Beth D, AU - Brady,Rebecca C, AU - Galloway,David, AU - Gurwith,Marc, AU - Hall,Robert H, AU - Kessler,Robert A, AU - Lock,Michael, AU - Haney,Douglas, AU - Lyon,Caroline E, AU - Pasetti,Marcela F, AU - Simon,Jakub K, AU - Szabo,Flora, AU - Tennant,Sharon, AU - Levine,Myron M, Y1 - 2016/03/21/ PY - 2015/11/04/received PY - 2016/02/08/accepted PY - 2016/3/23/entrez PY - 2016/3/24/pubmed PY - 2017/10/28/medline KW - challenge KW - cholera KW - efficacy KW - vaccine KW - volunteer SP - 1329 EP - 1335 JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America JO - Clin. Infect. Dis. VL - 62 IS - 11 N2 - 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. SN - 1537-6591 UR - https://www.unboundmedicine.com/medline/citation/27001804/Single_dose_Live_Oral_Cholera_Vaccine_CVD_103_HgR_Protects_Against_Human_Experimental_Infection_With_Vibrio_cholerae_O1_El_Tor_ L2 - https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/ciw145 DB - PRIME DP - Unbound Medicine ER -