title: Vibriocidal antibody responses to a bivalent killed whole-cell oral cholera vaccine in a phase III trial in Kolkata, India.
abstract: BACKGROUND
  During the development of a vaccine, identification of the correlates of protection is of paramount importance for establishing an objective criterion for the protective performance of the vaccine. However, the ascertainment of correlates of immunity conferred by any vaccine is a difficult task.
  
  
  METHODS
  While conducting a phase three double-blind, cluster-randomized, placebo-controlled trial of a bivalent killed whole-cell oral cholera vaccine in Kolkata, we evaluated the immunogenicity of the vaccine in a subset of participants. Randomly chosen participants (recipients of vaccine or placebo) were invited to provide blood samples at baseline, 14 days after the second dose and one year after the first dose. At these time points, serum geometric mean titers (GMT) of vibriocidal antibodies and seroconversion rates for vaccine and placebo arms were calculated and compared across the age strata (1 to 5 years, 5 to 15 years and more than 15 years) as well as for all age groups.
  
  
  RESULTS
  Out of 137 subjects included in analysis, 69 were vaccinees and 68 received placebo. There were 5•7 and 5•8 geometric mean fold (GMF) rises in titers to Vibrio cholerae Inaba and Ogawa, respectively at 14 days after the second dose, with 57% and 61% of vaccinees showing a four-fold or greater titer rise, respectively. After one year, the titers to Inaba and Ogawa remained 1•7 and 2•8 fold higher, respectively, compared to baseline. Serum vibriocidal antibody response to V. cholerae O139 was much lower than that to Inaba or Ogawa. No significant differences in the GMF-rises were observed among the age groups.
  
  
  CONCLUSIONS
  The reformulated oral cholera vaccine induced a statistically significant anti-O1 Inaba and O1 Ogawa vibriocidal antibody response 14 days after vaccination, which although declined after one year remained significantly higher than baseline. Despite this decline, the vaccine remained protective five years after vaccination.
authors.affiliation: Department of Epidemiology, National Institute of Cholera and Enteric Diseases, Kolkata, West Bengal, India.
authors.forename: Suman
authors.initials: S
authors.lastname: Kanungo
authors.affiliation: University of the Philippines, National Institutes of Health, Manila, Philippines.
authors.forename: Anna Lena
authors.initials: AL
authors.lastname: Lopez
authors.affiliation: International Vaccine Institute, SNU Research Park, Nakseongdae-dong, Gwanak-gu, Seoul, Korea.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ali
authors.affiliation: Department of Epidemiology, National Institute of Cholera and Enteric Diseases, Kolkata, West Bengal, India.
authors.forename: Byomkesh
authors.initials: B
authors.lastname: Manna
authors.affiliation: International Vaccine Institute, SNU Research Park, Nakseongdae-dong, Gwanak-gu, Seoul, Korea.
authors.forename: Deok Ryon
authors.initials: DR
authors.lastname: Kim
authors.affiliation: Department of Epidemiology, National Institute of Cholera and Enteric Diseases, Kolkata, West Bengal, India.
authors.forename: Tanmay
authors.initials: T
authors.lastname: Mahapatra
authors.affiliation: University of Gothenburg, Gothenburg, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Holmgren
authors.affiliation: Shantha Biotechnics Limited, Hyderabad, Andhra Pradesh, India.
authors.forename: Mandeep S
authors.initials: MS
authors.lastname: Dhingra
authors.affiliation: International Vaccine Institute, SNU Research Park, Nakseongdae-dong, Gwanak-gu, Seoul, Korea.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Weirzba
authors.affiliation: Executive Director, Translational Health Science and Technology Institute, Gurgaon, Haryana, India.
authors.forename: G Balakrish
authors.initials: GB
authors.lastname: Nair
authors.affiliation: Senior Scientist Platinum Jubilee Fellow, The National Academy of Sciences, Allahabad, India.
authors.forename: Sujit K
authors.initials: SK
authors.lastname: Bhattacharya
authors.affiliation: Executive Director, International Centre for Diarrheal Disease Research, Dhaka, Bangladesh.
authors.forename: John D
authors.initials: JD
authors.lastname: Clemens
authors.affiliation: Department of Epidemiology, National Institute of Cholera and Enteric Diseases, Kolkata, West Bengal, India.
authors.forename: Dipika
authors.initials: D
authors.lastname: Sur
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000907:Antibodies, Bacterial / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D002771:Cholera / Q000276:immunology*; D022121:Cholera Vaccines / Q000276:immunology*; D004311:Double-Blind Method; D006801:Humans; D007194:India; D007223:Infant; D014611:Vaccination / Q000379:methods; D014734:Vibrio cholerae / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D022121:Cholera Vaccines