A Study to Evaluate Safety and Immunogenicity of the Bivalent Killed Whole Cell Oral Cholera Vaccine in Adults and Children
Condition: Vibrio Cholerae
MeSH terms: Cholera
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to determine whether the killed bivalent (O1 and O139)whole cell
      oral cholera vaccine(Shanchol™) is safe and effective in the treatment of Vibrio cholerae.
    

Detailed description: 
      Provision of safe water and food, establishment of adequate sanitation, and implementation of
      personal and community hygiene constitute the main public health interventions against
      cholera. These measures cannot be implemented fully in the near future in most
      cholera-endemic areas. Improvements to water and sanitation require substantial long-term
      investments, commitment from the local government, and often take years to implement. In the
      meantime, a safe, effective and affordable vaccine would be a useful tool for cholera
      prevention and control.

      Considerable progress has been made during the last decade in the development of new
      generation oral vaccines against cholera. These have already been licensed in some countries
      and are now being considered for wider public health application. Cholera immunization is now
      recommended for travelers to high risk areas, refugee camps and for outbreak response.
      Furthermore, expanded use of cholera vaccines may be recommended for endemic areas, where
      there is increasing demand from both low- and middle-income populations.

      Starting in the mid-1980s, following technology transfer from Prof Jan Holmgren, Vietnamese
      scientists at the National Institute of Hygiene and Epidemiology (NIHE) in Hanoi developed
      and produced an oral, killed cholera vaccine for the country's public health programs. A
      two-dose regimen of a first generation monovalent (anti-O1) cholera vaccine produced at US$
      0.10 per dose underwent a field trial in Hue, Vietnam. The study was not formally randomized:
      the vaccine was assigned on the basis of a systematic allocation scheme and the control group
      did not receive a placebo. The calculated efficacy against El Tor cholera was 66% in fully
      immunized adults and children. Protection against non-cholera was assessed and none was found
      suggesting a non-biased study design. Subsequently, killed 0139 whole cells were added to the
      Vietnamese vaccine due to the emergence of the new form of epidemic cholera caused by this
      serogroup. A study found the bivalent vaccine to be safe and immunogenic in adults and
      children one year and older.

      The Vietnamese vaccine has several distinct advantages over the Swedish vaccine. The
      Vietnamese vaccine confers protection against the El Tor biotype in younger children. And the
      price of US $0.10 per dose is feasible for public health programs in developing countries,
      while the Swedish vaccine is prohibitively expensive. Finally, it can be administered without
      a buffer, while the Swedish vaccine requires a buffer and stricter cold chain requirements.

      Since licensure of the oral cholera vaccine in Vietnam, more than 9 million doses have been
      administered without any report of serious adverse events. The vaccine is produced according
      to recommended guidelines at the Company for Vaccine and Biological Production No. 1
      (VABIOTECH) in Hanoi. VABIOTECH is working towards WHO Good Manufacturing Practices (GMP)
      certification, which they hope to receive in the next few years. At the same time, the IVI
      and VABIOTECH have been working to internationalize the Vietnamese vaccine for global use. In
      order to comply with WHO requirements, the vaccine was reformulated.

      Phase II trials of this reformulated killed oral cholera vaccine were performed in SonLa,
      Vietnam and Kolkata, India where the vaccine was found to be safe and no serious adverse
      reaction was associated with the vaccine. The vaccine elicited significant vibriocidal
      antibody responses among vaccinees. In SonLa, 90% of adult recipients seroconverted to V.
      cholerae O1 following receipt of two doses of the vaccine. In Kolkata, 53% of adults and 80%
      of children aged 1-17 years developed 4-fold and greater rises in vibriocidal antibodies to
      V. cholerae O1. Data from Vietnam and India suggest that greater magnitudes in the
      vibriocidal responses following 2 doses of the vaccine are elicited compared to previous
      formulations. It has been suggested that this response may correlate with the higher
      lipopolysaccharide content of the vaccine, a result of changes in its standardization.

      A phase III trial of this vaccine is currently underway in Wards 29, 30, and 33 of Kolkata,
      India. Since this trial is still ongoing, data regarding adverse events still has not been
      analyzed. As yet no serious adverse reaction has been directly attributed to the vaccine.
      Surveillance continues in these areas to determine the efficacy of the vaccine.

      Through an agreement negotiated by the IVI, VABIOTECH produced the bulk reformulated bivalent
      vaccine under quality conditions supervised by the IVI. Shantha Biotechnics of India filled
      and finished the bulk, and obtained regulatory clearance for use of the vaccine in Phase II
      and III trials in India. In return, the technology for future production of the oral killed
      bivalent cholera vaccine was transferred to Shantha Biotechnics.
    

Intervention name(s): killed bivalent (O1 and O139)whole cell oral cholera vaccine
Intervention type(s): Biological
Intervention description(s): 1.5 ml given twice orally, 14 days apart
Other intervention name(s): Shanchol™
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: cholera; vibrios; oral cholera vaccine