title: Flexibility of oral cholera vaccine dosing-a randomized controlled trial measuring immune responses following alternative vaccination schedules in a cholera hyper-endemic zone.
abstract: BACKGROUND
  A bivalent killed whole cell oral cholera vaccine has been found to be safe and efficacious for five years in the cholera endemic setting of Kolkata, India, when given in a two dose schedule, two weeks apart. A randomized controlled trial revealed that the immune response was not significantly increased following the second dose compared to that after the first dose. We aimed to evaluate the impact of an extended four week dosing schedule on vibriocidal response.
  
  
  RESULTS
  In this double blind randomized controlled non-inferiority trial, 356 Indian, non-pregnant residents aged 1 year or older were randomized to receive two doses of oral cholera vaccine at 14 and 28 day intervals. We compared vibriocidal immune responses between these schedules. Among adults, no significant differences were noted when comparing the rates of seroconversion for V. cholerae O1 Inaba following two dose regimens administered at a 14 day interval (55%) vs the 28 day interval (58%). Similarly, no differences in seroconversion were demonstrated in children comparing the 14 (80%) and 28 day intervals (77%). Following 14 and 28 day dosing intervals, vibriocidal response rates against V. cholerae O1 Ogawa were 45% and 49% in adults and 73% and 72% in children respectively. Responses were lower for V. cholerae O139, but similar between dosing schedules for adults (20%, 20%) and children (28%, 20%).
  
  
  CONCLUSIONS
  Comparable immune responses and safety profiles between the two dosing schedules support the option for increased flexibility of current OCV dosing. Further operational research using a longer dosing regimen will provide answers to improve implementation and delivery of cholera vaccination in endemic and epidemic outbreak scenarios.
authors.affiliation: Division of Epidemiology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Suman
authors.initials: S
authors.lastname: Kanungo
authors.affiliation: Development and Delivery Unit, International Vaccine Institute, Seoul, Republic of Korea.
authors.forename: Sachin N
authors.initials: SN
authors.lastname: Desai
authors.affiliation: Division of Bacteriology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Ranjan Kumar
authors.initials: RK
authors.lastname: Nandy
authors.affiliation: Division of Clinical Medicine, National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Mihir Kumar
authors.initials: MK
authors.lastname: Bhattacharya
authors.affiliation: Development and Delivery Unit, International Vaccine Institute, Seoul, Republic of Korea.
authors.forename: Deok Ryun
authors.initials: DR
authors.lastname: Kim
authors.affiliation: Division of Bacteriology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Sinha
authors.affiliation: Division of Epidemiology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Tanmay
authors.initials: T
authors.lastname: Mahapatra
authors.affiliation: Laboratory Science Division, International Vaccine Institute, Seoul, Republic of Korea.
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Yang
authors.affiliation: University of the Philippines Manila, National Institutes of Health, Manila, Philippines.
authors.forename: Anna Lena
authors.initials: AL
authors.lastname: Lopez
authors.affiliation: Division of Data Management, National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Byomkesh
authors.initials: B
authors.lastname: Manna
authors.affiliation: Division of Data Management, National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Barnali
authors.initials: B
authors.lastname: Bannerjee
authors.affiliation: Development and Delivery Unit, International Vaccine Institute, Seoul, Republic of Korea; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States of America.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ali
authors.affiliation: Clinical Research and Development, Shantha Biotechnics Private Limited, Hyderabad, India.
authors.forename: Mandeep Singh
authors.initials: MS
authors.lastname: Dhingra
authors.affiliation: Department of Physiology, Calcutta University, Kolkata.
authors.forename: Ananga Mohan
authors.initials: AM
authors.lastname: Chandra
authors.affiliation: Office of the Executive Director, International Centre for Diarrheal Disease Research, Bangladesh; Department of Epidemiology, University of California Los Angeles Fielding School of Public Health, Los Angeles, United States of America.
authors.forename: John D
authors.initials: JD
authors.lastname: Clemens
authors.affiliation: Division of Epidemiology, National Institute of Cholera and Enteric Diseases, Kolkata, India; Office of the Scientific Director, PATH India Office, New Delhi, India.
authors.forename: Dipika
authors.initials: D
authors.lastname: Sur
authors.affiliation: Development and Delivery Unit, International Vaccine Institute, Seoul, Republic of Korea.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Wierzba
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D002771:Cholera / Q000453:epidemiology; D022121:Cholera Vaccines / Q000009:adverse effects / Q000276:immunology*; D004311:Double-Blind Method; D058872:Epidemics; D005260:Female; D006801:Humans; D007194:India / Q000453:epidemiology; D007223:Infant; D008297:Male; D014611:Vaccination; D014734:Vibrio cholerae / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D022121:Cholera Vaccines