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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a vaccine called Vivotif, designed to prevent typhoid, a serious illness that spreads through contaminated food and water. Researchers aim to understand how this vaccine aids the immune system in fighting typhoid and possibly other similar diseases. Participants will provide samples, such as blood and saliva, over several years to gather this information. Those in good health without issues like diabetes or heart problems in the past five years may be suitable for this trial. As a Phase 4 trial, the treatment has FDA approval and proven effectiveness, and this research seeks to understand how it benefits more patients.

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 is the safety track record for the Vivotif Typhoid Oral Vaccine?

Research has shown that the Vivotif oral typhoid vaccine is very safe and easy to handle. Studies have found that side effects are rare and usually mild. Most side effects, such as an upset stomach or headache, resolve on their own. The FDA has already approved Vivotif for travelers, indicating it has been tested and used widely, which adds to the confidence in its safety. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard injectable vaccines for typhoid, Vivotif is unique because it is an oral vaccine, which makes it easier to administer and potentially more appealing to people who are needle-averse. This oral vaccine contains live attenuated bacteria, which can stimulate a robust immune response. Researchers are excited about Vivotif because it has the potential to offer effective protection against typhoid fever through a simpler, less invasive method compared to traditional shots.

What is the effectiveness track record for the Vivotif Typhoid Oral Vaccine?

Research shows that the Vivotif oral vaccine, which participants in this trial will receive, helps protect against typhoid fever. Studies indicate that it benefits adults and children over six years old. The vaccine has proven to be 45% effective in preventing typhoid fever. For travelers, this moderate effectiveness supports its use and aligns with vaccination guidelines. This evidence highlights the vaccine's ability to lower the risk of typhoid, especially for those visiting areas where the disease is more common. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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]

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 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]

Citations

1. fda.gov fda.gov/media/75988/download

Vivotif® Typhoid Vaccine Live Oral Ty21a Results from clinical studies indicate that adults and children greater than 6 years of age may be protected against typhoid fever following the oral ingestion ...

2. vivotif.com vivotif.com/

Vivotif: Live Typhoid Vaccine Administered Orally Established Efficacy1. Results from clinical studies indicate that adults and children greater than 6 years of age may be protected against typhoid fever ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4604742/

Effectiveness of typhoid vaccination in US travelers - PMC We demonstrated moderate effectiveness of typhoid vaccination in US travelers, supporting vaccination recommendations.

4. thelancet.com thelancet.com/journals/langlo/article/PIIS2214-109X(23)00606-X/fulltext

Efficacy of typhoid vaccines against culture-confirmed ... The pooled efficacy against typhoid fever was 45% (95% CI 33–55%; four trials; 247 649 participants; I2 59%; moderate certainty) for Ty21a and 58% (44–69%; ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0264410X99002315

Duration of efficacy of Ty21a, attenuated Salmonella typhi ... Table 1 summarizes the efficacy data from the Area Occidente field trial showing efficacy over three doses of Ty21a in enteric-coated capsules given on an every ...

6. vivotif.com vivotif.com/consumer/

Consumer & Patient Information | Vivotif® Oral Typhoid Vaccine Don't let Typhoid Fever ruin your trip! Vivotif® is the only FDA-approved oral typhoid vaccine to help protect you while traveling abroad.

7. mayoclinic.org mayoclinic.org/drugs-supplements/typhoid-vaccine-live-oral-route/description/drg-20066578

Typhoid vaccine, live (oral route) - Side effects & dosage Typhoid vaccine taken by mouth helps prevent typhoid fever, but does not provide 100% protection.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5432773/

Overview of the impact of Typhoid and Paratyphoid fever. ... Thus, it is now accepted that the Ty21a vaccine is very safe and very well tolerated, and that adverse reactions are rare and self-limiting and consist of: ...