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

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

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).

Study Overview

• Status: Unknown
• Conditions: Healthy
• Intervention / Treatment: Biological: Vivotif; Biological: Typherix

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 Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sari H Pakkanen, MSc; Phone Number: +358405166165; Email: sari.pakkanen@helsinki.fi

Study Locations

• Finland
  • Helsinki, Finland, 00029
    • Active, not recruiting
    • Helsinki University Central Hospital
  • Helsinki, Finland, 00014
    • Active, not recruiting
    • University of Helsinki, Haartman Institute
  • Helsinki, Finland, 00100
    • Recruiting
    • Aava Medical Centre
    • Contact: Tuija Oksanen, Nurse; Email: tuija.oksanen@aava.fi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	Record adverse effects of the vaccines used	28 days

Collaborators and Investigators

• Sponsor: Helsinki University Central Hospital

Publications and helpful links

General Publications

• Pakkanen SH, Kantele JM, Savolainen LE, Rombo L, Kantele A. Specific and cross-reactive immune response to oral Salmonella Typhi Ty21a and parenteral Vi capsular polysaccharide typhoid vaccines administered concomitantly. Vaccine. 2015 Jan 9;33(3):451-8. doi: 10.1016/j.vaccine.2014.11.030. Epub 2014 Nov 26.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: December 30, 2013
• First Submitted That Met QC Criteria: April 19, 2014
• First Posted (Estimate): April 23, 2014

Study Record Updates

• Last Update Posted (Estimate): April 23, 2014
• Last Update Submitted That Met QC Criteria: April 19, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Salmonella Typhi; Vivotif; Typherix; non-typhoid Salmonella; Salmonella Paratyphi; enzyme-linked immunospot assay; Plasmablast
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterobacteriaceae Infections; Salmonella Infections; Typhoid Fever
• Other Study ID Numbers: Ty21a-ASC