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.
RCT Entities:
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: Wilbur H Chen; Richard N Greenberg; Marcela F Pasetti; Sofie Livio; Michael Lock; Marc Gurwith; Myron M Levine Journal: Clin Vaccine Immunol Date: 2013-10-30
Authors: C O Tacket; M B Cohen; S S Wasserman; G Losonsky; S Livio; K Kotloff; R Edelman; J B Kaper; S J Cryz; R A Giannella; G Schiff; M M Levine Journal: Infect Immun Date: 1999-12 Impact factor: 3.441
Authors: G Balakrish Nair; Firdausi Qadri; Jan Holmgren; Ann-Mari Svennerholm; Ashrafus Safa; Nurul A Bhuiyan; Q Shafi Ahmad; Shah M Faruque; A S G Faruque; Yoshifumi Takeda; David A Sack Journal: J Clin Microbiol Date: 2006-09-06 Impact factor: 5.948
Authors: M L Clements; M M Levine; C R Young; R E Black; Y L Lim; R M Robins-Browne; J P Craig Journal: J Infect Dis Date: 1982-04 Impact factor: 5.226
Authors: Dipika Sur; R Leon Ochiai; Sujit K Bhattacharya; Nirmal K Ganguly; Mohammad Ali; Byomkesh Manna; Shanta Dutta; Allan Donner; Suman Kanungo; Jin Kyung Park; Mahesh K Puri; Deok Ryun Kim; Dharitri Dutta; Barnali Bhaduri; Camilo J Acosta; John D Clemens Journal: N Engl J Med Date: 2009-07-23 Impact factor: 91.245
Authors: Loraine V Fabri; Kristy I Azzopardi; Joshua Osowicki; Hannah R Frost; Pierre R Smeesters; Andrew C Steer Journal: BMC Infect Dis Date: 2021-05-21 Impact factor: 3.090
Authors: Douglas J Haney; Michael D Lock; Marc Gurwith; Jakub K Simon; Glenn Ishioka; Mitchell B Cohen; Beth D Kirkpatrick; Caroline E Lyon; Wilbur H Chen; Marcelo B Sztein; Myron M Levine; Jason B Harris Journal: Vaccine Date: 2018-04-11 Impact factor: 3.641
Authors: DeAnna J Friedman-Klabanoff; Matthew B Laurens; Andrea A Berry; Mark A Travassos; Matthew Adams; Kathy A Strauss; Biraj Shrestha; Myron M Levine; Robert Edelman; Kirsten E Lyke Journal: Am J Trop Med Hyg Date: 2019-03 Impact factor: 2.345
Authors: Jeffrey P Kahn; Leslie Meltzer Henry; Anna C Mastroianni; Wilbur H Chen; Ruth Macklin Journal: Proc Natl Acad Sci U S A Date: 2020-10-29 Impact factor: 11.205
Authors: Leslie M Mayo-Smith; Jakub K Simon; Wilbur H Chen; Douglas Haney; Michael Lock; Caroline E Lyon; Stephen B Calderwood; Beth D Kirkpatrick; Mitchell Cohen; Myron M Levine; Marc Gurwith; Jason B Harris Journal: Clin Vaccine Immunol Date: 2017-01-05
Authors: Brandon Sit; Bolutife Fakoya; Ting Zhang; Gabriel Billings; Matthew K Waldor Journal: Proc Natl Acad Sci U S A Date: 2021-02-16 Impact factor: 11.205
Authors: Marie-Astrid Hoogerwerf; Jan Pieter R Koopman; Marijke C C Langenberg; Jacqueline J Janse; Janneke Kos-van Oosterhoud; Carola Feijt; Simon P Jochems; Claudia J de Dood; Roos van Schuijlenburg; Arifa Ozir-Fazalalikhan; Mikhael D Manurung; Erliyani Sartono; Martha T van der Beek; Béatrice M F Winkel; Petra H Verbeek-Menken; Koen A Stam; Fijs W B van Leeuwen; Pauline Meij; Angela van Diepen; Lisette van Lieshout; Govert J van Dam; Paul L A M Corstjens; Cornelis H Hokke; Maria Yazdanbakhsh; Leo G Visser; Meta Roestenberg Journal: Nat Med Date: 2020-02-17 Impact factor: 53.440