Clinical trial NCT02121145: Cross-reactive Immunity Elicited by Oral and Parenteral Typhoid Vaccines
Official title: Cross-reactive Immunity Elicited by Oral and Parenteral Typhoid Vaccines Against Non-typhoid Salmonellae
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Healthy
Keywords: Vivotif
Typherix
Salmonella Typhi
non-typhoid Salmonella
Salmonella Paratyphi
enzyme-linked immunospot assay
Plasmablast
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
First posted: 2014-04-23
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of circulating plasmablasts specific to various Salmonella strains
timeFrame: 7 days
Secondary outcomes:
measure: Level of serum antibodies specific to various Salmonella strains
timeFrame: 28 days
Other outcomes:
measure: Safety
timeFrame: 28 days
Locations:
city: Helsinki
country: Finland
facility: University of Helsinki, Haartman Institute
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Helsinki
country: Finland
facility: Aava Medical Centre
Study officials:
affiliation: Helsinki University Central Hospital
name: Anu Kantele, Assoc. prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.