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

87 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-label, non-randomized study. The purpose of this study is to better understand how vaccines against typhoid fever affect the normal immune system and bacteria in the intestine. Patients having standard-of-care colonoscopies will be divided into 3 groups: Group 1: Vivotif typhoid vaccination then colonoscopy; Group 2: Colonoscopy, then Vivotif typhoid vaccination, then follow-up colonoscopy; Group 3: Colonoscopy without vaccination. The Vivotif typhoid vaccine used in this study is licensed by the Food and Drug Administration (FDA) for travelers to developing countries. Volunteers will be asked to donate tissue, blood, saliva and stool samples for studying how the body responds to the typhoid vaccine.

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 data supports the effectiveness of the drug Vivotif Typhoid Oral Vaccine?

Research shows that the Vivotif vaccine, when tested in a large field trial in Chile, provided a 70% protection rate against typhoid fever over four years. Another trial in Egypt showed even higher effectiveness, with about 95% protection, indicating that the vaccine can be highly effective in preventing typhoid fever. ^{1 2 3 4 5}

Is the Typhoid Vaccine Live Oral Ty21a (Vivotif) safe for humans?

The Typhoid Vaccine Live Oral Ty21a (Vivotif) is generally well tolerated with infrequent and mild side effects, though there have been rare cases of severe allergic reactions (anaphylaxis). ^{1 2 3 5 6}

How is the Vivotif typhoid vaccine different from other typhoid treatments?

Vivotif is unique because it is an oral vaccine that uses a live, weakened strain of the bacteria to prevent typhoid fever, unlike traditional vaccines that are injected. It acts as a 'magic shield' by inducing an immune response before infection occurs, and it can also be used to deliver other antigens, making it versatile. ^{1 2 3 5 7}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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]

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 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 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 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]

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. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

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

6. 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]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Vaccination against typhoid fever: present status. [2018]