Typhoid Vaccine for Typhoid

Overseen By Robin Barnes, CRNP

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Maryland, Baltimore

Must not be taking: Corticosteroids, others

Disqualifiers: Pregnancy, Crohn's, Ulcerative colitis, 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: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a typhoid vaccine affects the immune system and gut bacteria. It involves three groups: one receives the Vivotif Typhoid Oral Vaccine (a live oral vaccine) before a colonoscopy, another after, and the last undergoes a colonoscopy without the vaccine. Participants provide tissue, blood, saliva, and stool samples for research. This trial suits healthy individuals scheduled for a colonoscopy at the University of Maryland. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, offering participants a chance to contribute to understanding its broader benefits.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immune suppressive medications, you may not be eligible to participate.

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

Research has shown that the Vivotif Typhoid Oral Vaccine is generally safe. This FDA-approved vaccine helps prevent typhoid fever. Studies have found it to be well-tolerated by adults and children over 6 years old, with most experiencing no serious side effects.

Some individuals might have mild reactions, such as stomach pain, nausea, or a rash, but these side effects usually don't last long. It's important to remember that no vaccine offers 100% protection. However, Vivotif has effectively protected many people from typhoid fever.

Overall, evidence suggests that the Vivotif vaccine is a safe choice for preventing typhoid fever. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the Vivotif Typhoid Oral Vaccine because it offers a unique approach to studying immune responses directly at the mucosal level in the small intestine. Unlike traditional vaccines that focus solely on preventing typhoid fever, this trial combines the vaccine with colonoscopy procedures to obtain detailed insights into how the immune system and gut microbiota interact with the vaccine. By collecting biopsies and other specimens during colonoscopies, researchers aim to uncover new information about the body's defense mechanisms, potentially leading to more effective vaccines or treatment strategies for typhoid and other intestinal diseases.

What is the effectiveness track record for the Vivotif typhoid vaccine?

Research shows that the Vivotif typhoid oral vaccine effectively protects against typhoid fever. Studies have found that both adults and children over six years old benefit from this vaccine. It triggers a strong immune response, helping to prevent intestinal fever. Although not 100% effective, it offers good protection, especially for travelers. The FDA has approved this vaccine, confirming its safety and effectiveness for this use. In this trial, participants will receive the Vivotif vaccine in various contexts related to colonoscopy procedures to study immune responses and microbiota at the mucosal level. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are healthy and undergoing a colonoscopy for colorectal cancer screening at the University of Maryland. They must be able to give consent and not have a history of certain bowel diseases, bleeding disorders, or immune suppression from illness or treatment. Pregnant or nursing women and those with past allergic reactions to the typhoid vaccine cannot participate.

Inclusion Criteria

I am scheduled for a colonoscopy at the University of Maryland for cancer screening.

Provide written informed consent prior to initiation of any study procedures

Healthy, as defined by considered fit to undergo outpatient elective colonoscopy by the referring health care provider

Exclusion Criteria

I have a bleeding disorder that prevents safe biopsy procedures.

Pregnancy or nursing mother

You had an allergic reaction to a typhoid vaccine that you took by mouth in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination and Colonoscopy

Participants receive Vivotif typhoid vaccination followed by a colonoscopy to collect tissue, blood, saliva, and stool samples.

4 weeks

1 visit (in-person)

Follow-up Colonoscopy

Participants undergo a follow-up colonoscopy to collect additional specimens and assess immune response.

4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for immune response and microbiome changes post-vaccination.

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Vivotif Typhoid Oral Vaccine

Trial Overview

The study investigates how the Vivotif typhoid oral vaccine affects the body's immune system and gut bacteria in people getting colonoscopies. Participants will be split into three groups: one receiving vaccination before colonoscopy, another after colonoscopy with follow-up, and a third having just the colonoscopy.

How Is the Trial Designed?

Group I: Vaccination, Colonoscopy Experimental Treatment 1 Intervention

Individuals receive immunization with Vivotif typhoid vaccine prior to routine colonoscopy examination. During colonoscopy, small bowel biopsies will be obtained to examine immune responses and microbiota at the mucosal level; brushings will also be obtained.

Group II: Colonoscopy, Vacciniation, Colonoscopy Experimental Treatment 1 Intervention

Individuals receive immunization with Vivotif typhoid vaccine after initial colonoscopy exam and specimen collection and prior to a routine follow up colonoscopy examination during which additional specimens will be collected.

Group III: Colonoscopy Without Vaccination Active Control 1 Intervention

Individuals do not receive immunization but consent to collection of specimens during colonoscopy. The specimens to be collected in all three groups include stool, saliva, and small bowel biopsies (terminal ileum).

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

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 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 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]

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 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 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]

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]

Citations

1.

vivotif.com

vivotif.com/

Vivotif: Live Typhoid Vaccine Administered Orally

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.

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 ...

3.

pmc.ncbi.nlm.nih.gov

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

Overview of the impact of Typhoid and Paratyphoid fever. ...

Vivotif appears to be a powerful means of preventing enteric fever. Indeed, over the years it has proved efficacious, eliciting a triple immunologic response.

4.

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.

5.

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.

6.

vivotif.com

vivotif.com/consumer/

Consumer & Patient Information | Vivotif® Oral Typhoid Vaccine

VIVOTIF may help provide protection against typhoid fever for at least 5 years. · VIVOTIF is the only FDA-approved oral vaccine for typhoid fever. · All 4 doses ...