Safety and Immunogenicity of a Killed Oral Cholera Vaccine in Infants
Safety and Immunogenicity of a Killed Oral Cholera Vaccine in Infants
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).
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.
Inclusion Criteria, Infants 10 weeks to 6 months of age at Day 0:

 -  Healthy infants aged from birth to 2 months who have not received OPV1, DTP1 or HepB2
 will be recruited in Kolkata, North 24 Parganas, and South 24 Parganas

 -  All subjects must satisfy the following criteria at study entry:

 1. Male or female infants aged from birth to 2 months who the investigator believes
 will comply with the requirements of the protocol (i.e., available for follow-up
 visits and specimen collection)

 2. Written informed consent obtained from their parents/guardians

 3. Healthy subjects as determined by:

 -  Medical history

 -  Physical examination

 -  Clinical judgment of the investigator

 Inclusion Criteria, Infants 9 months to less than 12 months

 -  Healthy infants aged from 9 months to less than 12 months who have not received
 measles vaccine will be recruited in Kolkata, North 24 Parganas, and South 24 Parganas

 -  All subjects must satisfy the following criteria at study entry:

 1. Male or female infants aged from 9 months to less than 12 months who the
 investigator believes will comply with the requirements of the protocol (i.e.,
 available for follow-up visits and specimen collection)

 2. Written informed consent obtained from their parents/guardians

 3. Healthy subjects as determined by:

 -  Medical history

 -  Physical examination

 -  Clinical judgment of the investigator

 Exclusion Criteria, Infants 10 weeks to 6 months of age at Day 0:

 1. Ongoing serious chronic disease

 2. Immunocompromising condition or therapy

 3. Diarrhea (having more frequent watery stools than usual within a 24 hour period) 6
 weeks prior to enrollment

 4. Intake of any anti-diarrheal medicine in the past week

 5. Irritability, loss of appetite, general ill-feeling or vomiting in the past 24 hours

 6. Acute disease one week prior to enrollment, with or without fever. Temperature =>38C
 (oral) or axillary temperature =>37.5C warrants deferral of the vaccination pending
 recovery of the subject

 7. Receipt of antibiotics in past 14 days

 8. Receipt of killed oral cholera vaccine

 9. Receipt of live or killed enteric vaccine in 2 months

 10. Receipt of DTwP1, OPV1 or Hepatitis B2 vaccines

 11. One or two episodes of diarrhea lasting for more than 2 weeks in the past 2 months

 12. One or two episodes of abdominal pain lasting for more than 2 weeks in the past 2
 months

 13. Z-score of < -2 on the weight for age WHO Child Growth Standards

 Exclusion Criteria, Infants 9 months to less than 12 months:

 1. Ongoing serious chronic disease

 2. Immunocompromising condition or therapy

 3. Diarrhea (3 or more loose/watery stools within a 24 hour period) 6 weeks prior to
 enrollment

 4. Intake of any anti-diarrheal medicine in the past week

 5. Abdominal pain/cramps, loss of appetite, general ill-feeling or vomiting in the past
 24 hours

 6. Acute disease one week prior to enrollment, with or without fever. Temperature =>38C
 (oral) or axillary temperature =>37.5C warrants deferral of the vaccination pending
 recovery of the subject

 7. Receipt of antibiotics in past 14 days

 8. Receipt of killed oral cholera vaccine

 9. Receipt of live or killed enteric vaccine in last 4 weeks

 10. Receipt of measles-containing vaccine (MCV)

 11. One or two episodes of diarrhea lasting for more than 2 weeks in the past 6 months

 12. One or two episodes of abdominal pain lasting for more than 2 weeks in the past 6
 months

 13. Disease episode potentially related to measles

 14. receipt of blood, blood products or a parenteral immunoglobulin preparation in past 3
 months

 15. History of anaphylaxis, any serious vaccine reaction, allergy to eggs, egg products or
 to any measles vaccine component

 16. Any condition which in the opinion of the investigator might interfere with the
 evaluation of the study objectives

 17. Z-score of < -2 on the weight for age WHO Child Growth Standards