Safety, Immunogenicity and Compatibility With DTP of a Typhoid Fever Vaccine in Infants

Phase 2

Completed

Conditions: Typhoid Fever

Interventions: Biological: DTP
Biological: Vi-rEPA conjugate vaccine for typhoid fever
Biological: Hib-TT

Registration Number: NCT00342628

Lead Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Brief Summary: The purpose of this study is to evaluate the safety, immunogenicity, and compatibility of our Vi-rEPA conjugate administered to infants with their routine vaccinations.

We propose to recruit 300 full term healthy newborns in Vietnam and randomly divide them to receive Vi-rEPA plus DTP, Hib-TT (not yet used in Vietnam) plus DTP, or DTP alone. Consent is obtained following interviews of mothers during prenatal visits, or after delivery. All vaccines will be administered at 2, 4, and 6 months. A booster of Vi-rEPA or Hib-TT conjugate will be administered at 12 months of age and reactions monitored at 6, 24 and 48 hours after each injection. Maternal and cord blood samples are collected during labor and at delivery. Blood will be taken at 7, and 12 months of age from all study infants and at 13 months from infants injected with Vi-rEPA or with Hib-TT at 12 months. The blood samples will be assayed for Vi, Hib, diphtheria, tetanus and pertussis antibodies.

The levels of serum IgG anti-Vi elicited by Vi-rEPA administered to infants by the above schedule will be compared to those elicited by this vaccine in 2 to 5 year-olds in the efficacy trial conducted in Dong Thap Province, Vietnam.

Detailed Description: Typhoid fever remains common, serious, and difficult-to-treat throughout the world including Vietnam. Limitations of the three licensed typhoid vaccines have prevented their use for routine vaccination of infants. The most recent, Vi polysaccharide typhoid vaccine is useful only in individuals greater than or equal to 5 years of age because of its age-related and T-cell independent properties. The immunogenicity of Vi in individuals less than 5 years-old has been improved by binding it to a protein. In 2 to 4-year-olds, 2 injections of the Vi conjugate induced higher levels of serum IgG anti-Vi than Vi in 5 to 14-year-olds.

A double-blind, placebo controlled and randomized efficacy study in 2 -to-5 years old children in Vietnam showed an over-all efficacy after 27 months of active surveillance followed by 19 months of passive surveillance of 89%. Subsequently a dosage study in the same age group showed the highest antibody levels were induced by the 25 mcg dose.

Now we wish to evaluate the safety, immunogenicity, and compatibility of our Vi-rEPA conjugate administered to infants with their routine vaccinations.

We propose to recruit 300 full term healthy newborns in Vietnam and randomly divide them to receive Vi-rEPA plus DTP (Group A), Hib-TT (not yet used in Vietnam) plus DTP (Group B), or DTP alone (Group C). Maternal and cord blood are taken routinely on all deliveries in Vietnam; these sera will be retrieved for storage when consent is obtained following interviews of mothers during prenatal visits, or after delivery. All vaccines will be administered at 2, 4, and 6 months. A booster of Vi-rEPA or Hib-TT conjugate will be administered at 12 months of age and reactions monitored at 6, 24 and 48 hours after each injection. Blood will be taken at 7, and 12 months of age from all study infants and at 13 months from infants injected with Vi-rEPA or with Hib-TT at 12 months. The blood samples will be assayed for Vi, Hib, diphtheria, tetanus and pertussis antibodies.

The levels of serum IgG anti-Vi elicited by Vi-rEPA administered to infants by the above schedule will be compared to those elicited by this vaccine in 2 to 5 year-olds in the efficacy trial conducted in Dong Thap.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 301

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EPI	DTP	DTP at 2,4 and 6 months
Vi-rEPA plus DTP	Vi-rEPA conjugate vaccine for typhoid fever	Vi-rEPA and DTP at 2, 4, 6 months, and Vi-rEPA at 12 months
Vi-rEPA plus DTP	DTP	Vi-rEPA and DTP at 2, 4, 6 months, and Vi-rEPA at 12 months
Hib-TT plus DTP	Hib-TT	Hib-TT and DTP at 2,4 and 6 months, Hib-TT at 12 months
Hib-TT plus DTP	DTP	Hib-TT and DTP at 2,4 and 6 months, Hib-TT at 12 months

Primary Outcome Measures

Name	Time	Method
Number of Infants With Adverse Reactions After Vaccination	at 2, 4, 6 and 12 months	Number of infants with Fever\>=38.0 C, Induration\>=2.5cm at DTP site, Induration\>=2.5cm,Vi-rEPA/Hib-TT site, Erythema\>=2.5cm, at DTP site, Erythema\>=2.5cm, Vi-rEPA/Hib-TT site, Inconsolable crying\<4hr, Inconsolable crying\>=4hr per injection with Vi conjugate vaccine given in conjunction with DTP in infants.

Secondary Outcome Measures

Name	Time	Method
IgG Anti-Vi Levels	cord sera, infants' sera at 7, 12 and 13 months	IgG anti-Vi was measured by ELISA and expressed as ELISA units (EU)in all sera.
Antibody Responses to Tetanus Toxoid, Diphtheria Toxoid, and Pertussis Toxin	Cord sera, and infants' sera at 7, 12 and 13 months of age	IgG anti-diphtheria toxoid (DT), -tetanus toxoid (TT) and -pertussis toxin (PT) were measured by ELISA in sera of 30 randomly chosen infants per group.
Antibody Responses to Hib CP	Cord sera and infant sera at 7, 12, and 13 months	IgG anti-Hib CP was measured by ELISA in sera of 30 randomly chosen infants per group