title: Safety and immunogenicity of a live oral recombinant cholera vaccine VA1.4: a randomized, placebo controlled trial in healthy adults in a cholera endemic area in Kolkata, India.
abstract: BACKGROUND
  A live oral cholera vaccine VA 1.4 developed from a non-toxigenic Vibrio cholerae O1 El Tor strain using ctxB gene insertion was further developed into a clinical product following cGMP and was evaluated in a double-blind randomized placebo controlled parallel group two arm trial with allocation ratio of 1∶1 for safety and immunogenicity in men and women aged 18-60 years from Kolkata, India.
  
  
  METHODS
  A lyophilized dose of 1.9×109 CFU (n = 44) or a placebo (n = 43) reconstituted with a diluent was administered within 5 minutes of drinking 100 ml of a buffer solution made of sodium bicarbonate and ascorbic acid and a second dose on day 14.
  
  
  RESULTS
  The vaccine did not elicit any diarrhea related adverse events. Other adverse events were rare, mild and similar in two groups. One subject in the vaccine group excreted the vaccine strain on the second day after first dose. The proportion of participants who seroconverted (i.e. had 4-folds or higher rise in reciprocal titre) in the vaccine group were 65.9% (95% CI: 50.1%-79.5%) at both 7 days (i.e. after 1st dose) and 21 days (i.e. after 2nd dose). None of the placebo recipients seroconverted. Anti-cholera toxin antibody was detected in very few recipients of the vaccine.
  
  
  CONCLUSIONS
  This study demonstrates that VA 1.4 at a single dose of 1.9×109 is safe and immunogenic in adults from a cholera endemic region. No additional benefit after two doses was seen.
  
  
  BACKGROUND
  Clinical Trials Registry-India, National Institute of Medical Statistics (Indian Council of Medical Research) CTRI/2012/04/002582.
authors.affiliation: Department of Epidemiology, National Institute of Cholera & Enteric Diseases, Kolkata, West Bengal, India.
authors.forename: Suman
authors.initials: S
authors.lastname: Kanungo
authors.affiliation: Society for Applied Studies, Kolkata, West Bengal, India.
authors.forename: Bandana
authors.initials: B
authors.lastname: Sen
authors.affiliation: Department of Microbiology, National Institute of Cholera & Enteric Diseases, Kolkata, West Bengal, India.
authors.forename: Thandavarayan
authors.initials: T
authors.lastname: Ramamurthy
authors.affiliation: Department of Epidemiology, National Institute of Cholera & Enteric Diseases, Kolkata, West Bengal, India.
authors.forename: Dipika
authors.initials: D
authors.lastname: Sur
authors.affiliation: Department of Epidemiology, National Institute of Cholera & Enteric Diseases, Kolkata, West Bengal, India.
authors.forename: Byomkesh
authors.initials: B
authors.lastname: Manna
authors.affiliation: Department of Microbiology, National Institute of Cholera & Enteric Diseases, Kolkata, West Bengal, India.
authors.forename: Gururaja P
authors.initials: GP
authors.lastname: Pazhani
authors.affiliation: Department of Microbiology, National Institute of Cholera & Enteric Diseases, Kolkata, West Bengal, India.
authors.forename: Goutam
authors.initials: G
authors.lastname: Chowdhury
authors.affiliation: Department of Microbiology, National Institute of Cholera & Enteric Diseases, Kolkata, West Bengal, India.
authors.forename: Puja
authors.initials: P
authors.lastname: Jhunjhunwala
authors.affiliation: Department of Microbiology, National Institute of Cholera & Enteric Diseases, Kolkata, West Bengal, India.
authors.forename: Ranjan K
authors.initials: RK
authors.lastname: Nandy
authors.affiliation: Department of Microbiology, National Institute of Cholera & Enteric Diseases, Kolkata, West Bengal, India.
authors.forename: Hemanta
authors.initials: H
authors.lastname: Koley
authors.affiliation: Department of Epidemiology, National Institute of Cholera & Enteric Diseases, Kolkata, West Bengal, India.
authors.forename: Mihir Kumar
authors.initials: MK
authors.lastname: Bhattacharya
authors.affiliation: Catalyst Clinical Services Pvt. Ltd., Delhi, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Catalyst Clinical Services Pvt. Ltd., Delhi, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Goel
authors.affiliation: Department of Biotechnology, Ministry of Science and Technology, New Delhi, India.
authors.forename: Bindu
authors.initials: B
authors.lastname: Dey
authors.affiliation: Institute of Post Graduate Medicine and Research, Chandigarh, India.
authors.forename: Thungapathra
authors.initials: T
authors.lastname: M
authors.affiliation: Translational Health Science and Technology Institute, Gurgaon, Haryana, India.
authors.forename: G Balakrish
authors.initials: GB
authors.lastname: Nair
authors.affiliation: Department of Microbiology, National Institute of Cholera & Enteric Diseases, Kolkata, West Bengal, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Society for Applied Studies, Kolkata, West Bengal, India.
authors.forename: Dilip
authors.initials: D
authors.lastname: Mahalanabis
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000276:immunology; D002771:Cholera / Q000276:immunology / Q000517:prevention & control*; D022121:Cholera Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014734:Vibrio cholerae
chemical_list: D000907:Antibodies, Bacterial; D022121:Cholera Vaccines; D014614:Vaccines, Synthetic