Ty21a-ASC: Cross-reactive Immunity Elicited by Oral and Parenteral Typhoid Vaccines

Sponsor

Helsinki University Central Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT02121145

Collaborator

(none)

100

Enrollment

Locations

Arms

Duration (Months)

33.3

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Healthy	Biological: Vivotif Biological: Typherix	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Study Start Date :

Oct 1, 2013

Anticipated Primary Completion Date :

Dec 1, 2019

Anticipated Study Completion Date :

Dec 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vivotif + Typherix primary immunization Vivotif + Typherix primary immunization	Biological: Vivotif 3 oral doses Biological: Typherix one intramuscular dose
Experimental: Vivotif booster Volunteers previously immunized with Vivotif, now receiving a Vivotif secondary immunization	Biological: Vivotif 3 oral doses
Experimental: Typherix booster Volunteers previously immunized with Typherix, now receiving a Typherix secondary immunization	Biological: Typherix one intramuscular dose
Experimental: Vivotif + Typherix booster Volunteers previously immunized with Vivotif and Typherix, now receiving Vivotif and Typherix as secondary immunization	Biological: Vivotif 3 oral doses Biological: Typherix one intramuscular dose

Outcome Measures

Primary Outcome Measures

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

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

Other Outcome Measures

Safety [28 days]
Record adverse effects of the vaccines used

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 64 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	University of Helsinki, Haartman Institute	Helsinki	Finland	00014
2	Helsinki University Central Hospital	Helsinki	Finland	00029
3	Aava Medical Centre	Helsinki	Finland	00100