Safety and Immunogenicity of a Killed Oral Cholera Vaccine in Infants
- Conditions
- CholeraVibrio InfectionsDiarrhea
- Interventions
- Biological: Killed Escherichia coli K12 placeboBiological: Bivalent killed oral cholera vaccine
- Registration Number
- NCT00548054
- Lead Sponsor
- International Vaccine Institute
- Brief Summary
In order to assess whether the bivalent killed oral cholera vaccine may be used safely among infants who are most at risk for cholera, the investigators need to determine the safety and immunogenicity of the killed oral cholera vaccine among infants less than 1 year of age when given with the expanded program on immunization (EPI) vaccines including diptheria, pertussis and tetanus (DPT), oral polio vaccine (OPV), Hepatitis B vaccines and measles vaccine. Furthermore, the investigators also need to make sure that immune interference does not occur among all the other vaccine antigens given at the same time. Findings from this study will pave the way for the possible use of the killed whole cell oral cholera vaccine (OCV).
- Detailed Description
Cholera is an important public health problem worldwide, remaining endemic in most of the developing world at the same time causing outbreaks in areas where lapses in sanitation occur.
A monovalent (anti-O1) oral killed cholera vaccine with a B-subunit was developed by Professor Jan Holmgren in Sweden and is now licensed to a pharmaceutical company in the United Kingdom. The technology for this vaccine was transferred to Vietnamese scientists at the National Institute of Hygiene and Epidemiology in Hanoi in the mid-1980s.
The Vietnamese developed a bivalent vaccine, with killed 0139 cells and without the B-subunit. Since licensure, more than 9 million doses have been given without any report of serious adverse events.
The vaccine has been reformulated in order to internationalize the vaccine. Phase II trials of this vaccine in Son La, Vietnam and Kolkata, India have found the vaccine to be safe with no serious adverse reactions associated with the vaccine. A phase III study of the reformulated vaccine is ongoing in Kolkata, India.
The youngest person the vaccine has been administered to was a 1 year old. Previous studies with the B-subunit containing killed whole cell vaccine was found to be safe among infants as young as 6 months eliciting significant vibriocidal responses among 53% of vaccinees. However, no data is available regarding the use of the bivalent whole cell killed oral vaccine in infants.
Due to the higher risk of cholera among infants, the possibility of introducing cholera vaccine as part of the expanded programme on immunization (EPI) needs to be investigated.
Data regarding the safety and immunogenicity of the reformulated bivalent killed whole cell vaccine among infants needs to be gathered in order to pave the way for the possible use of this vaccine in cholera-endemic areas where infants and children are most at risk. Furthermore, there is no data regarding the concomitant use of this vaccine with other EPI vaccines given to young infants such as Diphtheria-Tetanus-whole cell Pertussis (DTwP), Oral Polio Vaccine (OPV) Hepatitis B and Measles vaccines. It would be important to determine if interference exists between the killed whole cell vaccine and other antigens included in the regular EPI schedule. Providing the killed whole cell vaccine in the context of the EPI will make it easier to introduce cholera vaccines in areas which are cholera-endemic.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 300
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Placebo Group for EPI Assay Killed Escherichia coli K12 placebo Placebo bled at day 56 for EPI immunogenicity testing Vaccine Group for Vibriocidal and Measles Assay Bivalent killed oral cholera vaccine Killed whole cell cholera vaccine bled at day 14 and 28 for measles immunogenicity testing Vaccine Group for Vibriocidal Assay Bivalent killed oral cholera vaccine Killed whole cell cholera vaccine bled at day 42 for vibriocidal assay Vaccine Group for EPI Assay Bivalent killed oral cholera vaccine Killed whole cell cholera vaccine bled at day 56 for EPI immunogenicity testing Placebo Group for Vibriocidal Assay Killed Escherichia coli K12 placebo Placebo bled at day 42 for vibriocidal assay Placebo Group for Vibriocidal and Measles Assay Killed Escherichia coli K12 placebo Placebo bled at day 14 and 28 for measles immunogenicity testing
- Primary Outcome Measures
Name Time Method Safety: proportion of subjects with diarrhea entire study period Immunogenicity: proportion of subjects exhibiting 4-fold or greater rises in titers of serum vibriocidal antibodies, relative to baseline 14 days after each dose
- Secondary Outcome Measures
Name Time Method Proportion of subjects with any of the following: a) immediate reactions 30 minutes and up to 3 days after each dose, b) serious adverse events occurring during the trial, c) any adverse event entire study period Proportion of subjects with ≥ 0.1 mIU/ml of anti-tetanus toxoid antibodies 28 days after the third DPT dose For initially seronegative subjects: proportion of subjects with ≥ 15 EU/ml of anti-pertussis IgG and for initially seropositive subjects, proportion with antibody titers equal to or greater than the initial titers prior to vaccination 28 days after DPT dose Proportion of subjects with ≥ 0.1 mIU/ml of anti-diphtheria toxoid antibodies 28 days after the third DPT dose Proportion of subjects with ≥ 8 fold dilution of anti-polio virus 1, 2, or 3 antibodies by micro-neutralization test 28 days after the fourth dose of OPV Proportion of subjects with >150 mIU/ml measles IgG antibodies 28 days after single dose of measles vaccine Proportion of subjects with ≥ 10 mIU/ml of anti-HbS antibody 28 days after the third dose of Hepatitis B vaccine Geometric mean serum vibriocidal titers 14 days after each dose
Trial Locations
- Locations (1)
National Institute of Cholera and Enteric Disease
🇮🇳Kolkata, West Bengal, India