Safety and Immunogenicity of Locally Manufactured New (HL-OCV) Oral Cholera Vaccine
Safety and Immunogenicity of Locally Manufactured New (HL-OCV) Oral Cholera Vaccine
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).
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.
Inclusion Criteria:

 1. Age: 1years to less than 5 years for the younger children group; 5- less than18 years
 for older children and adolescent group and 18- 45 years (inclusive) for the adult
 group.

 2. Sex: Male, Female, Transgender.

 3. Consent: Informed consent from study participants and guardian in case of children
 along with assent in children 11-17 years (inclusive) of age.

 4. Apparently healthy.

 Exclusion Criteria:

 1. Suffering from diarrhoea or abdominal pain or vomiting in the past 24 hours or
 diarrhoea lasting for more than 2 weeks in the past 6 months

 2. History of taking oral cholera vaccine.

 3. History of taking any other live or killed enteric vaccine in the last 8 weeks.

 4. History of anaphylaxis or serious vaccine reaction.

 5. Currently use of any immunosuppressive or immune-modifying drugs.

 6. Receipt of blood or blood products or parenteral immunoglobulin preparation in the
 past 3 months.

 7. Currently on antimicrobial therapy (taking antibiotics within 24 hours during
 screening and vaccination).

 8. Severe malnutrition defined as wt-for-ht z-score <-3.0 with or without oedema.

 9. For married females pregnancy or plans to become pregnant during the study period (as
 determined by verbal screening) will be excluded. In addition, pregnancy test will be
 done by pregnancy strip test before each day of vaccination (Day 0 and day 14) for
 married female.

 10. Culture positive V. cholerae, ETEC, Salmonella and Shigella in stool.