Immune Response Elicited by Concomitant Administration of Oral Typhoid Fever (Vivotif®) and Cholera (Dukoral®) Vaccines

The goal of this clinical trial is to explore the coadministration of oral typhoid fever (Vivotif®) and cholera (Dukoral®) vaccines in healthy volunteers aged 18-65 years. The main question it aims to answer is:

• Does coadministration impact the immune responses to Vivotif® and Dukoral® vaccines

Participants will:

• receive either oral typhoid fever (Vivotif®) or oral cholera (Dukoral®) vaccines or both simultaneously
• give blood samples for immunogenicity analyses
• participate in adverse event follow up

Researchers will compare those receiving only one of the vaccines to those receiving both simultaneously to see if coadministration has an impact on antigen-specific responses measured with:

• ELISPOT (plasmablast responses specific to Salmonella typhi, Vibrio Cholerae and Enterotoxigenic Escherichia coli)
• ELISA (antibodies in lymphocyte supernatants (ALS) and serum antibodies specific to vaccine antigens)

Study Overview

• Status: Completed
• Conditions: Cholera; Typhoid Fever; Vaccine-Preventable Diseases
• Intervention / Treatment: Biological: Oral typhoid fever vaccine; Biological: Oral cholera vaccine

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 4

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland, 00290
    • Meilahti Vaccine Research Center, Helsinki University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

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 (14 days before immunization to day 28 ± 3). Abstinence is acceptable.
5. Available for all visits scheduled in this study.

Exclusion Criteria:

1. Vaccination against typhoid fever or cholera within 5 years before dosing.
2. History of clinical typhoid fever or cholera.
3. Immunization with any other vaccine (oral or parenteral) within 4 weeks prior to study period or vaccination planned during it.
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 immunemodifying drugs within 6 months before the first dose of IMP; oral corticosteroids in dosages of ≥0.5 mg/kg/d prednisolone or equivalent are excluded; inhaled or topical steroids allowed.
6. Acute or chronic clinically significant gastrointestinal disease.
7. Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
8. Pregnancy or lactation.
9. Acute disease at the time of enrolment (defined as the presence of a moderate or severe illness with or without fever (fever defined as body temperature of ≥38 °C).
10. Alcohol or drug abuse.
11. Suspected non-compliance.
12. Use of any investigational drug or vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
13. Any clinically significant history of known or suspected anaphylaxis or hypersensitivity reaction based on the judgement of the investigator.
14. Employee at the investigational site or relative or spouse of the investigator.
15. Any other criteria which, in the investigator's opinion, would compromise the ability of a subject to participate in the study, a subject's well-being, or the outcome of the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vivotif; Three oral doses of typhoid fever vaccine (Vivotif®).	Biological: Oral typhoid fever vaccine; Oral typhoid fever vaccine (Vivotif®) on Days 0, 2 and 4.; Other Names: Vivotif®
Active Comparator: Dukoral; Two oral doses of cholera vaccine (Dukoral®).	Biological: Oral cholera vaccine; Oral cholera vaccine (Dukoral®) on Days 0 and 7.; Other Names: Dukoral®
Experimental: Dukoral+Vivotif; Oral typhoid fever and cholera vaccines (Vivotif® and Dukoral®) administered simultaneously.	Biological: Oral typhoid fever vaccine; Oral typhoid fever vaccine (Vivotif®) on Days 0, 2 and 4.; Other Names: Vivotif®; Biological: Oral cholera vaccine; Oral cholera vaccine (Dukoral®) on Days 0 and 7.; Other Names: Dukoral®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Magnitude of antigen-specific plasmablast responses to oral typhoid fever (Vivotif®) and cholera (Dukoral®) vaccines (ASCs/million PBMCs)	Measurement of IgA -, IgG- and IgM-secreting antibody cells (ASC ELISPOT) specific to Salmonella typhi (whole cell), Vibrio cholerae (whole cell and CTB-toxin) and Enterotoxigenic Escherichia coli (ETEC whole cell and LTB-toxin).	Blood samples on Days 0-7 for all participants and Days 12-14 for participants in Dukoral and Dukoral+Vivotif arms.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Titer of antigen-specific antibodies in lymphocyte supernatants (ALS) to oral typhoid fever (Vivotif®) and cholera (Dukoral®) vaccines.	Measurement of anti-salmonella, anti-cholera and anti-ETEC antibodies in ALS samples (ELISA)	Blood samples on Days 0-7 for all participants and Days 12-14 for participants in Dukoral and Dukoral+Vivotif arms.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Titer of antigen-specific serum antibodies to oral typhoid fever (Vivotif®) and cholera (Dukoral®) vaccines.	Measurement of anti-salmonella, anti-cholera and anti-ETEC antibodies in serum (ELISA)	Blood samples on Days 0 and 28 ± 3 for all participants.

Collaborators and Investigators

• Sponsor: Helsinki University Central Hospital
• Collaborators: University of Helsinki
• Investigators: Principal Investigator: Anu Kantele, MD, PhD, Meilahti Vaccine Research Center, MeVac, Helsinki University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2023
• Primary Completion (Actual): June 26, 2024
• Study Completion (Actual): June 26, 2024

Study Registration Dates

• First Submitted: October 23, 2023
• First Submitted That Met QC Criteria: October 23, 2023
• First Posted (Actual): October 27, 2023

Study Record Updates

• Last Update Posted (Estimated): December 5, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Immunogenicity; ELISPOT; Salmonella Typhi; B cells; Coadministration; Oral vaccination; Vibrio cholerae
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Body Temperature Changes; Enterobacteriaceae Infections; Vibrio Infections; Salmonella Infections; Vaccine-Preventable Diseases; Fever; Cholera; Typhoid Fever; Immunologic Factors; Physiological Effects of Drugs; Vaccines
• Other Study ID Numbers: Dukoral+Vivotif

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The decision to share IPD will be done when the study is completed. IPD can be shared only if it does not compromise the anonymity of the study participants.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No