Cross-reactive Immunity Elicited by Oral and Parenteral Typhoid Vaccines

Study Overview
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Brief Summary
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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
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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.

Official Title
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Cross-reactive Immunity Elicited by Oral and Parenteral Typhoid Vaccines Against Non-typhoid Salmonellae

Conditions
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Healthy

Intervention / Treatment
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* Biological: Vivotif
* Biological: Typherix


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects aged ≥18 to ≤65 years General good health as established by medical history and physical examination Written informed consent Females of childbearing potential must agree to use an efficacious hormonal or barrier method of birth control during the study. Abstinence is acceptable. Available for all visits scheduled in this study. Exclusion Criteria: Primary groups: Vaccination against typhoid fever within 5 years before dosing. History of clinical typhoid fever, clinical paratyphoid A or B fever. Immunization with any other vaccine (oral or parenteral) within 4 weeks prior to study start or planned vaccination during the study Current intake of antibiotics or end of antibiotic therapy <8 days before first IMP administration 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 Acute or chronic clinically significant gastrointestinal disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vivotif + Typherix primary immunization<br>Vivotif + Typherix primary immunization | Biological: Vivotif<br>* 3 oral doses<br>Biological: Typherix<br>* one intramuscular dose<br>|
| Experimental: Vivotif booster<br>Volunteers previously immunized with Vivotif, now receiving a Vivotif secondary immunization | Biological: Vivotif<br>* 3 oral doses<br>|
| Experimental: Typherix booster<br>Volunteers previously immunized with Typherix, now receiving a Typherix secondary immunization | Biological: Typherix<br>* one intramuscular dose<br>|
| Experimental: Vivotif + Typherix booster<br>Volunteers previously immunized with Vivotif and Typherix, now receiving Vivotif and Typherix as secondary immunization | Biological: Vivotif<br>* 3 oral doses<br>Biological: Typherix<br>* one intramuscular dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of circulating plasmablasts specific to various Salmonella strains | To study whether cross-reactive immune response is similar if the two vaccines are given simultaneously after booster immunization than after primary immunization | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of serum antibodies specific to various Salmonella strains | To study whether cross-reactive serum immune response is similar if the two vaccines are given simultaneously after booster immunization than after primary immunization | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vivotif, Typherix, Salmonella Typhi, non-typhoid Salmonella, Salmonella Paratyphi, enzyme-linked immunospot assay, Plasmablast