Vivotif Vaccine for Typhoid Risk Reduction

Overseen By Susan Holian, RN

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Maryland, Baltimore

Must not be taking: Anti-malarial drugs

Disqualifiers: Diabetes, Cancer, Heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

150 Participants Needed

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.

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

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

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Findings from Research

In a study of 115 travelers, 68% reported complete compliance with all dosing and storage recommendations for the Ty21a typhoid vaccine, but electronic monitoring revealed only 53% adherence, highlighting the importance of accurate compliance assessment methods.

Despite many travelers not following all guidelines, the vaccine's viability was not significantly affected by storage conditions, as no differences were found compared to controls, suggesting that the vaccine remains effective even with some temperature excursions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compliance to live oral Ty21a typhoid vaccine, and its effect on viability. Stubi, CL., Landry, PR., Pétignat, C., et al.[2022]

The live oral typhoid vaccine Vivotif (Salmonella typhi Ty 21a) has been shown to be well tolerated in volunteer studies and large-scale trials, but its efficacy varied based on the formulation used, particularly in how it withstands stomach acid.

A revised acid-resistant capsule formulation demonstrated a 70% protection rate in a field trial with 44,000 school-age children in Chile, and a new lyophilized formulation is currently being tested, which previously showed 95% efficacy in an Egyptian trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness of oral, attenuated live Salmonella typhi Ty 21a vaccine in controlled field trials]. Cryz, SJ., Fürer, E., Levine, MM.[2006]

The Typhoid Vaccine Live Oral Ty21a (Vivotif) is generally well tolerated, with adverse events being infrequent and mild, but a case of anaphylaxis has been reported following its administration.

In this case, a 66-year-old male experienced anaphylaxis after the third dose of the vaccine, highlighting the need for monitoring and preparedness for rare but serious allergic reactions during vaccination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case report of anaphylaxis to Typhoid Vaccine Live Oral Ty21a (Vivotif). Haas, NL., Haas, MRC., Gregory, C.[2018]

The oral live vaccine Ty21a has shown over 60% protection against typhoid fever after 7 years, making it a strong candidate for public health programs in developing countries.

The Vi polysaccharide vaccine also demonstrated more than 65% protection, with sustained antibody levels after 3 years, but both vaccines require further safety and efficacy evaluations, especially in young children and in relation to other vaccines like measles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccination against typhoid fever: present status. Ivanoff, B., Levine, MM., Lambert, PH.[2018]

The Ty21a strain of Salmonella typhi, used in the Vivotif vaccine, acts as a preventive measure against typhoid fever by inducing specific immune responses rather than treating the disease after infection.

Ty21a can also be utilized as a carrier for delivering other antigens, enhancing its potential for vaccine development through efficient protein secretion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vivotif--a 'magic shield' for protection against typhoid fever and delivery of heterologous antigens. Gentschev, I., Spreng, S., Sieber, H., et al.[2009]

In a study of 1.9 million military personnel vaccinated against Salmonella Typhi, the intramuscular Vi capsule vaccine was administered to 94.3% of recipients, showing a higher rate of nausea, headache, and fever compared to the oral Vivotif vaccine, although overall adverse event rates were low.

The oral Vivotif vaccine was associated with higher rates of rash and non-infectious diarrhea, indicating that while both vaccines are effective, they have different safety profiles that may influence choice in vaccination strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccination of active component US military personnel against Salmonella Typhi. Porter, CK., Sorrell, T., Mitra, I., et al.[2017]

The live attenuated vaccine Ty800, derived from Salmonella typhi Ty2, was found to be safe in human volunteers, with only mild side effects reported and no serious adverse events like bacteremia.

Ty800 elicited strong intestinal immune responses in 10 out of 11 subjects, indicating high immunogenicity, and produced IgG responses comparable to those seen in control subjects vaccinated with the standard Ty21a vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

phoP/phoQ-deleted Salmonella typhi (Ty800) is a safe and immunogenic single-dose typhoid fever vaccine in volunteers. Hohmann, EL., Oletta, CA., Killeen, KP., et al.[2019]

References

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

Compliance to live oral Ty21a typhoid vaccine, and its effect on viability. [2022]

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

[Effectiveness of oral, attenuated live Salmonella typhi Ty 21a vaccine in controlled field trials]. [2006]

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

A case report of anaphylaxis to Typhoid Vaccine Live Oral Ty21a (Vivotif). [2018]

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

Vaccination against typhoid fever: present status. [2018]

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

Vivotif--a 'magic shield' for protection against typhoid fever and delivery of heterologous antigens. [2009]

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

Vaccination of active component US military personnel against Salmonella Typhi. [2017]

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]