Vivotif Vaccine for Typhoid Risk Reduction

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: University of Maryland, Baltimore

Must not be taking: Anti-malarial drugs

Disqualifiers: Diabetes, Cancer, Heart disease, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial involves giving volunteers an oral vaccine called Vivotif to protect against typhoid fever. The study focuses on travelers to developing countries who are at higher risk of the disease. The vaccine helps the body learn to fight off typhoid bacteria. Researchers will collect samples from participants over time to understand how the vaccine works and if it can help with other similar diseases.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are currently being treated with anti-malarial drugs, you would be excluded from participating.

What data supports the effectiveness of the Vivotif drug for reducing the risk of typhoid?

Research shows that the Vivotif vaccine, which is an oral live vaccine, provided a protection rate of 70% in a large field trial in Chile involving 44,000 children over four years. Additionally, a similar formulation showed approximately 95% efficacy in an Egyptian field trial. ^{1 2 3 4 5}

Is the Vivotif Typhoid Oral Vaccine generally safe for humans?

The Vivotif Typhoid Oral Vaccine is generally well tolerated with infrequent and mild side effects, though there has been a rare case of a severe allergic reaction (anaphylaxis) reported. ^{1 2 3 6 7}

How does the Vivotif drug differ from other typhoid fever treatments?

Vivotif is unique because it is an oral live-attenuated vaccine, meaning it uses a weakened form of the bacteria to stimulate immunity, and is taken by mouth rather than by injection. This makes it different from the Typhim Vi vaccine, which is given as an injection and uses a different part of the bacteria to protect against typhoid fever. ^{1 2 3 4 6}

Eligibility Criteria

Adults over 18 in good health can join this trial. They must not have heart disease, active ulcers, intestinal conditions, recent anemia treatment, substance abuse issues, diabetes or recent cancer (except certain skin and cervical cancers). Blood tests will exclude those with abnormal blood counts or liver function, hepatitis B/C or HIV infections. Pregnant women and those on anti-malarial drugs cannot participate.

Inclusion Criteria

Informed, written consent

I am 18 years old or older.

I was found to be in good health during a check-up within the last 28 days.

Exclusion Criteria

You currently have a problem with drugs or alcohol.

I have been hospitalized more than 3 times for serious infections like pneumonia or meningitis.

I have been treated for anemia in the past 6 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination

Volunteers receive immunization with Vivotif oral typhoid vaccine

1 day

1 visit (in-person)

Specimen Collection

Blood, saliva, and stool specimens are collected at subsequent visits

up to 8 years

Follow-up

Participants are monitored for safety and effectiveness after vaccination

approximately 5 years

Treatment Details

Interventions

• Vivotif Typhoid Oral Vaccine (Vaccine)

Trial Overview The study involves the Vivotif typhoid oral vaccine already approved for travelers to certain countries. Participants will receive the vaccine and provide blood, saliva, and stool samples for up to eight years to help researchers understand how it protects against other similar diseases.

Participant Groups

Group I: Vaccination with Oral Typhoid Vaccine (Vivotif) Experimental Treatment 1 Intervention

Volunteers receive immunization with Vivotif oral typhoid vaccine. Blood, saliva, and stool specimens are collected at subsequent visits.

Vivotif Typhoid Oral Vaccine is already approved in United States for the following indications:

🇺🇸 Approved in United States as Vivotif for:

• Immunization against disease caused by Salmonella typhi for travelers to areas where there is a recognized risk of exposure to S. typhi, persons with intimate exposure to an S. typhi carrier, and microbiology laboratorians who work frequently with S. typhi

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Maryland, Baltimore, Center for Vaccine Development and Global Health Baltimore, MD

Who Is Running the Clinical Trial?

University of Maryland, Baltimore Lead Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

Compliance to live oral Ty21a typhoid vaccine, and its effect on viability. [2022] Concerns have been expressed that in travelers the efficacy of the live oral Ty21a typhoid vaccine Vivotif could be lower than reported, maybe due to a lack of compliance. The purpose of this study was to examine the level of compliance with the recommendations regarding dosing, timing of dosing with respect to food intake, and storage.

2. Switzerland pubmed.ncbi.nlm.nih.gov

[Effectiveness of oral, attenuated live Salmonella typhi Ty 21a vaccine in controlled field trials]. [2006] The first live oral typhoid vaccine (strain Salmonella typhi Ty 21a) distributed under the trade name of "Vivotif" has been evaluated for safety and efficacy in volunteer studies and in large-scale, placebo-controlled, double-blind field trials. While the data demonstrated that the vaccine was well tolerated, the level of efficacy varied distinctly. It is probable that the differences observed can be chiefly attributed to the various vaccine formulations evaluated to facilitate the passage of the acid-sensitive vaccine strain through the acid environment of the stomach. Based upon these results, the initially marketed formulation (2 bicarbonate capsules + vaccine capsule) was changed to an acid-resistant capsule which was subsequently evaluated in a field trial conducted in Chile and involving 44,000 school age children. Following 4 years of surveillance, a protection rate of 70% was obtained. To further optimize the means of delivering the vaccine, a formulation consisting of lyophilized vaccine reconstituted in a buffer solution is now being evaluated in a Chilean and Indonesian field trial. A similar though less practicable formulation showed excellent efficacy (approximately 95%) in a previous Egyptian field trial.

3. England pubmed.ncbi.nlm.nih.gov

A case report of anaphylaxis to Typhoid Vaccine Live Oral Ty21a (Vivotif). [2018] Typhoid Vaccine Live Oral Ty21a (Vivotif) is typically well tolerated, and adverse events are infrequent and mild. To the best of the authors' knowledge, only one prior anaphylactic reaction has previously been reported. We present a case of anaphylaxis related to Vivotif, in which a 66-year-old male with no medical comorbidities developed anaphylaxis following the third of a four-dose course (in the absence of concomitant vaccination administration), which consisted of tongue swelling, difficulty breathing, abdominal discomfort and rash. He was managed with epinephrine, corticosteroids and antihistamines.

4. Switzerland pubmed.ncbi.nlm.nih.gov

Vaccination against typhoid fever: present status. [2018] Typhoid fever remains an underestimated important health problem in many developing countries, causing more than 600,000 deaths annually in the world. Because of the reactogenicity of the parenteral, killed whole-cell vaccine, research has been oriented towards vaccination orally using live organisms and purified antigen. Live vaccine Ty21a, given by the oral route, has been extensively tested in several studies in developing countries. Its liquid formulation was the most effective, providing more than 60% protection after 7 years of follow-up. A Vi polysaccharide vaccine has been elaborated and provided more than 65% protection; after 3 years of follow-up the Vi antibody level was still at a high level. These two vaccines are therefore candidates for use in public health control programmes. Before such use, however, they need further evaluation for safety and protective efficacy when administered to the EPI-targeted age groups. The question of whether typhoid fever vaccines interfere with the response to simultaneously administered measles vaccine must also be studied. New live vaccines, given by the oral route in one dose, have been constructed through genetic engineering. The first results are promising, but they must be improved before use in a large-scale study. These strains could be used as live vector to deliver foreign antigens to the intestinal mucosa.

5. Switzerland pubmed.ncbi.nlm.nih.gov

Vivotif--a 'magic shield' for protection against typhoid fever and delivery of heterologous antigens. [2009] The attenuated Salmonella typhi strain Ty21a is the main constituent of Vivotif, the only attenuated live oral vaccine against typhoid fever. In comparison with antibiotics, the 'magic bullets' which Paul Ehrlich was striving for to treat infectious diseases, this vaccine should be viewed as a 'magic shield', because rather than treating typhoid fever after the infection has started, immunisation with this vaccine strain prevents infection and disease by the induction of specific immune responses. Ty21a is also an attractive carrier for the delivery of heterologous antigens. Recently, we successfully used Ty21a for antigen delivery via the haemolysin secretion system of Escherichia coli, which allows efficient protein secretion from the carrier bacteria.

6. Netherlands pubmed.ncbi.nlm.nih.gov

Vaccination of active component US military personnel against Salmonella Typhi. [2017] Vaccination against Salmonella Typhi is one of the leading public health interventions reducing the risk of typhoid fever. There are two available licensed vaccines, Vivotif, oral live-attenuated, and Typhim Vi, intramuscular Vi capsular polysaccharide. The US military is a high risk travel population commonly vaccinated for S. Typhi. We describe the use of S. Typhi vaccination in this population and the acute reactogenicity profile of these vaccines.

7. United States pubmed.ncbi.nlm.nih.gov

phoP/phoQ-deleted Salmonella typhi (Ty800) is a safe and immunogenic single-dose typhoid fever vaccine in volunteers. [2019] The phoP/phoQ virulence regulatory genes of Salmonella typhi Ty2 were deleted, and the resultant strain (Ty800) was tested as a live attenuated typhoid fever vaccine in human volunteers. Groups of 2 or 3 subjects received single oral doses of 10(7), 10(8), 10(9), or 10(10) cfu. Two volunteers who received the largest dose had self-limited side effects; no bacteremias were detected. Ten of 11 subjects had evidence of intestinal immune responses to the vaccine as measured by increases in S. typhi lipopolysaccharide-specific IgA-secreting cells in peripheral blood samples. Humoral immune responses were measured and compared with those of control vaccinees who received 4 oral doses of S. typhi Ty21a. In the most sensitive assays, 9 of 11 volunteers and 5 of 8 Ty21a control vaccinees had evidence of IgG directed against S. typhi antigens. Ty800 is safe, and single oral doses are highly immunogenic in humans.