Cross-reactive Immunity Elicited by Oral and Parenteral Typhoid Vaccines

Phase 4

• Conditions: Healthy
• Interventions: Biological: Vivotif; Biological: Typherix

• Registration Number: NCT02121145
• Lead Sponsor: Helsinki University Central Hospital

Brief Summary

In a recent controlled study, the investigators explored cross-reactive immune responses against different Salmonella spp. in healthy volunteers immunized with either the oral (Vivotif® ) or parenteral (Typherix®) typhoid vaccines (ISRCTN68125331). In the present study immune responses will be studied in a group receiving both of these vaccines and in the previously immunized volunteers after booster immunization (same groups receive same vaccines 2-4 years after primary immunization).

Detailed Description

Many Salmonella spp causing gastroenteritis share O antigen serotypes with Salmonella enteritidis subsp. enterica serovar Typhi (S.typhi) and could therefore be in 'reach' of the protective efficacy of the oral live typhoid fever vaccine Vivotif®. Some of these Salmonellae are common causes of diarrhoea in travellers (0-30% of travellers diarrhea depending on the area). In a recent controlled study, the investigators showed that a cross-reactive immune response is elicited against different Salmonella spp. in healthy volunteers immunized with either the oral (Vivotif® ) or parenteral (Typherix®) typhoid vaccines (ISRCTN68125331).

In the present study immune responses will be studied in a group receiving both of these vaccines and in previously immunized volunteers after booster immunization (same groups receive same vaccines 2-4 years after primary immunization; groups: Vivotif / Typherix / Vivotif + Typherix). The results are compared to those obtained after primary immunization.

Study Timeline

• Study Start: 2013-10
• Study First Submitted: 2013-12-30
• Status Verified: 2014-04
• Study First Submitted QC: 2014-04-19
• Last Update Submitted: 2014-04-19
• Study First Posted: 2014-04-23
• Last Update Posted: 2014-04-23
• Primary Completion: 2019-12
• Study Completion: 2019-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Male or female subjects aged ≥18 to ≤65 years
2. General good health as established by medical history and physical examination
3. Written informed consent
4. Females of childbearing potential must agree to use an efficacious hormonal or barrier method of birth control during the study. Abstinence is acceptable.
5. Available for all visits scheduled in this study.

Exclusion Criteria

1. Primary groups: Vaccination against typhoid fever within 5 years before dosing.
2. History of clinical typhoid fever, clinical paratyphoid A or B fever.
3. Immunization with any other vaccine (oral or parenteral) within 4 weeks prior to study start or planned vaccination during the study
4. Current intake of antibiotics or end of antibiotic therapy <8 days before first IMP administration
5. Chronic (longer than 14 days) administration of immunosuppressants or other immune-modifying drugs within 6 months before the first dose of investigational vaccine; oral corticosteroids in dosages of ≥0.5 mg/kg/d prednisolone or equivalent are excluded; inhaled or topical steroids are allowed
6. Acute or chronic clinically significant gastrointestinal disease

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vivotif + Typherix primary immunization	Vivotif	Vivotif + Typherix primary immunization
Vivotif + Typherix primary immunization	Typherix	Vivotif + Typherix primary immunization
Typherix booster	Typherix	Volunteers previously immunized with Typherix, now receiving a Typherix secondary immunization
Vivotif booster	Vivotif	Volunteers previously immunized with Vivotif, now receiving a Vivotif secondary immunization
Vivotif + Typherix booster	Vivotif	Volunteers previously immunized with Vivotif and Typherix, now receiving Vivotif and Typherix as secondary immunization
Vivotif + Typherix booster	Typherix	Volunteers previously immunized with Vivotif and Typherix, now receiving Vivotif and Typherix as secondary immunization

Primary Outcome Measures

Name	Time	Method
Number of circulating plasmablasts specific to various Salmonella strains	7 days	To study whether cross-reactive immune response is similar; * if the two vaccines are given simultaneously; * after booster immunization than after primary immunization

Secondary Outcome Measures

Name	Time	Method
Level of serum antibodies specific to various Salmonella strains	28 days	To study whether cross-reactive serum immune response is similar; * if the two vaccines are given simultaneously; * after booster immunization than after primary immunization

Trial Locations

Locations (3)

Helsinki University Central Hospital; 🇫🇮 Helsinki, Finland

Aava Medical Centre; 🇫🇮 Helsinki, Finland

University of Helsinki, Haartman Institute; 🇫🇮 Helsinki, Finland