Safety and Immunogenicity of Locally Manufactured New (HL-OCV) Oral Cholera Vaccine
Condition: Cholera
MeSH terms: Cholera
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Cholera, a rapidly dehydrating watery diarrheal disease transmitted through water or food
      contaminated with the bacterium, Vibrio cholerae, is a major cause of morbidity and mortality
      in low income countries like Bangladesh. In our country, Cholera disease burden consists of
      both cholera outbreaks and endemic cholera comprising at least 300,000 severe cases and 1.2
      million infections each year. To combat this situation, Vaccination against cholera has been
      proved effective both in endemic and epidemic settings. But, the WHO recommended Dukoral and
      Prequalified Shanchol are quite expensive for our country perspective. Therefore, locally
      manufactured OCV can improve the cost effectiveness and make it affordable for all. The
      hypothesis of this proposal is that Locally produced orally administered whole cell
      inactivated HL-OCV test formulations A and B are safe and immunogenic in adults and children
      in Bangladesh as compared to ShancholTM. The results of the study will allow us to understand
      the safety and immunogenicity outcome of the HL-OCV compared to Shanchol vaccine. The total
      sample size will be 840 healthy participants. 840 healthy participants (360 adults, 240
      Children and Adolescent and 240 young children) of 18-45 years, 5- less than 18 years and 1
      year to less than 5 years will be enrolled in the study. Children whose parents/guardians
      give voluntary consent will be enrolled in the study. The investigators will provide 2 dose
      of vaccine for three groups in 14 days interval. Test formulations will be locally
      manufactured and the comparator group will get Shanchol. The Investigators propose to collect
      three blood samples (Day 0, 14 and 28).
    

Detailed description: 
      Background : Cholera continues to be a major cause of morbidity and mortality in low income
      countries including Bangladesh. It is estimated that there are at least 300,000 severe cases
      and over 4,500 deaths in Bangladesh each year1. The overall morbidity for cholera remains
      high. A global stockpile of OCV has been created by WHO in 2013 for epidemic and outbreak
      settings30. However, the global demand for the vaccine far exceeds the present supply for
      both epidemic and also endemic settings3. It can be envisioned that local production of an
      affordable OCV for high risk population in endemic settings will improve the present scenario
      in Bangladesh and other countries.

      Knowledge gap: The WHO recommends OCV for use in both endemic and epidemic cholera settings4.
      At present there are two vaccines that are WHO prequalified. These include Dukoral which is
      registered in Bangladesh and in over 50 countries. However, the disadvantage of use of
      Dukoral is that its current price is expensive for Bangladesh and other developing countries.
      In addition, the need for buffer to formulate the vaccine makes it less fieldable for mass
      vaccination programs.Another whole killed OCV, ShancholTM, which is WHO prequalified, is
      based on similar bacterial components as Dukoral and licensed in India but not in Bangladesh.
      Although this vaccine is relatively affordable it may not be sufficiently cost effective for
      the Government of Bangladesh to implement it in our poor endemic settings. At present, the
      vaccine is in short supply and will not be able to meet the global demands. In order to
      increase supply of OCV and make the vaccine more affordable, MSD Wellcome Trust Hilleman
      Labs. Pvt. Ltd in collaboration with Goteberg University, Sweden has engineered new oral
      cholera vaccine HL-OCV,consisting of formaldehyde-inactivated recombinant V.cholerae strain
      ,MS 1568 expressing both Ogawa and Inaba antigens. The vaccine formulation is quantified on
      total O1 lipopolysaccharide ,LPS content which is matched to that of ShancholTM ,not less
      than 600 mcg/ml LPS for O1; Formulation A and higher than Shanchol ,not less than 900 mcg/ml
      LPS for O1; Formulation B. The vaccine technology is transferred to local manufacturer
      ,INCEPTA in Bangladesh.

      Relevance: The study of this locally manufactured new HL-OCV, among children and adults will
      be able to give us information regarding the safety and immunogenicity of two different
      formulations of vaccine, based on LPS content. The study will not only identify safe
      formulation among the two formulation A or B, but will also be able to show superiority of
      higher LPS formulation in most naive population in children who are 1-5 years of age. Results
      of the study will be able to identify and select most suitable formulation in Phase II study
      for licensure in Bangladesh. This study will further pave the way forward for field studies
      which could establish field efficacy of vaccine compared to existing vaccines in Bangladesh.

      Hypothesis : Locally produced orally administered whole cell inactivated HL-OCV test
      formulations A and B are safe and immunogenic in adults and children in Bangladesh as
      compared to Shanchol TM.

      Objectives: The objective of this study is to determine most safe and immunogenic formulation
      for new oral cholera vaccine HL-OCV, and comparing with licensed vaccine ShancholTM.
    

Intervention name(s): HL-OCV; Shanchol
Intervention type(s): Biological; Biological
Intervention description(s): Pharmaceutical company in Bangladesh is now producing HL-OCV, with technological support from MSD wellcome trust Hilleman pt. ltd, which meets international Good manufacturing practice( GMP) standards and WHO production guidelines.; The vaccine is manufactured by Shantha Biotechnics in hyderabad, India and is prequalified by the WHO. Shanchol is available in a single dose. This vaccine is used as two dose regimen.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: cholera vaccine; hikojima serotype; randomized trial; immunogenicity