Typhoid and Cholera Vaccines for Immune Response

Overseen By Rosary Zara Necesario, RN

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Maryland, Baltimore

Disqualifiers: Pregnancy, Coagulopathy, Crohn's, Immunosuppression, 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

Compensation: Varies

Number of Visits: 5

240 Participants Needed

Trial Summary

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 on medications that cause immunosuppression, you may not be eligible to participate.

What data supports the effectiveness of the drug Vaxchora for immune response?

Vaxchora, a single-dose oral cholera vaccine, has been shown to protect against cholera infection in travelers, with studies indicating it provides protection 10 days and 3 months after vaccination. It is the first FDA-approved cholera vaccine in the U.S., offering a specific preventive measure for travelers to high-risk areas. ^{1 2 3 4 5}

Is the Typhoid and Cholera Vaccines treatment safe for humans?

The Vaxchora cholera vaccine is generally safe and has been approved by the FDA, with no adverse reactions reported in trials. The Vivotif typhoid vaccine is also typically well tolerated, though there has been a rare case of anaphylaxis (a severe allergic reaction) reported. ^{1 2 4 5 6}

How is the Vaxchora and Vivotif treatment different from other treatments for typhoid and cholera?

Vaxchora is unique because it is a single-dose, oral vaccine specifically approved for cholera prevention, making it convenient for travelers to high-risk areas. Unlike other cholera vaccines that require multiple doses, Vaxchora provides protection with just one dose, although it is age-restricted and requires reconstitution. ^{1 2 3 7 8}

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 and cholera affect the normal immune system and bacteria in the intestine. Patients having standard-of-care endoscopies (colonoscopy and/or esophagogastroduodenoscopy (EGD)) will be divided into 3 groups: Group 1: Vivotif typhoid vaccination and/or Vaxchora cholera vaccination then endoscopy Group 2: Endoscopy, then Vivotif typhoid vaccination and/or Vaxchora cholera vaccination, then follow-up endoscopy Group 3: Endoscopy without vaccination. Both vaccines used in this study are 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 and/or cholera vaccine.

Eligibility Criteria

This trial is for adults over 18 who are healthy and already scheduled for an EGD or colonoscopy at the University of Maryland Medical Center. They must be able to consent and not have Crohn's, ulcerative colitis, immunosuppression, recent vaccines, pregnancy, certain cancers, or a history of severe vaccine allergy.

Inclusion Criteria

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

Able to provide written informed consent prior to initiation of any study procedures

I am scheduled for an EGD or colonoscopy at the University of Maryland Medical Center.

Exclusion Criteria

I have a history of Crohn's disease or ulcerative colitis.

I have a condition or treatment that weakens my immune system, except for inactive non-melanoma skin cancer.

I haven't received any vaccines in the two weeks before getting Ty21a or CVD 103-HgR.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination and Endoscopy

Participants receive Vivotif typhoid vaccine and/or Vaxchora cholera vaccine followed by endoscopy to collect specimens and study immune responses

4-6 weeks

2 visits (in-person)

Endoscopy, Vaccination, Follow-up Endoscopy

Participants undergo initial endoscopy, receive vaccination, and then have a follow-up endoscopy to collect additional specimens

8-12 weeks

3 visits (in-person)

Follow-up

Participants are monitored for immune response and safety after vaccination and endoscopy

4 weeks

Treatment Details

Interventions

• Vaxchora
• Vivotif Typhoid Oral Vaccine

Trial Overview The study examines how typhoid (Vivotif) and cholera (Vaxchora) vaccines affect the immune system and gut bacteria. Participants will either receive vaccinations before or after their endoscopies or have an endoscopy without vaccination. Samples like tissue and blood will be collected.

Participant Groups

Group I: Vaccination, Endoscopy Experimental Treatment 2 Interventions

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

Group II: Endoscopy, Vaccination, Endoscopy Experimental Treatment 2 Interventions

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

Group III: Endoscopy Without Vaccination Active Control 1 Intervention

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

Vaxchora is already approved in United States for the following indications:

Approved in United States as Vaxchora for:

• Prevention of cholera

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Findings from Research

Vaxchora is a single-dose oral vaccine that provides 90.3% protection against cholera caused by V cholerae serogroup O1, based on human trials conducted before its FDA approval.

The vaccine is generally well-tolerated, with common side effects including fatigue, headache, and abdominal pain, but its safety and efficacy have not been established for children, immunocompromised individuals, or pregnant and breastfeeding women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaxchora: A Single-Dose Oral Cholera Vaccine. Cabrera, A., Lepage, JE., Sullivan, KM., et al.[2018]

Vaxchora is the first FDA-approved vaccine specifically designed to prevent cholera infection, which is particularly important for travelers visiting high-risk areas in Africa and Southeast Asia.

As a live attenuated, single-dose oral vaccine, Vaxchora offers a targeted prophylactic option against cholera, reducing the risk of severe diarrhea and dehydration caused by the bacterium Vibrio cholerae.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaxchora: The First FDA-Approved Cholera Vaccination in the United States. Mosley, JF., Smith, LL., Brantley, P., et al.[2020]

The oral cholera vaccine Vaxchora™ was licensed by the US FDA in 2016 and has been shown to effectively protect against cholera for at least 3 months after a single dose in US volunteers.

Despite its effectiveness, Vaxchora™ presents challenges for use in resource-poor settings due to requirements for reconstitution, age restrictions (18 to 64 years), lack of data in endemic populations, and issues with cold chain storage and cost.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An overview of VaxchoraTM, a live attenuated oral cholera vaccine. Saluja, T., Mogasale, VV., Excler, JL., et al.[2023]

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]

Two new typhoid vaccines have been developed—one for oral use and one for injection—that have fewer and milder side effects compared to older vaccines, improving safety for patients.

An oral cholera vaccine has been created that not only provides long-lasting protection against cholera without adverse reactions but also offers significant protection against diarrhea caused by enterotoxigenic E. coli (ETEC), showcasing its efficacy and cross-reactivity benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New vaccines against bacterial enteric infections. Holmgren, J., Svennerholm, AM.[2005]

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 cholera vaccine, which includes a nontoxic B subunit of cholera toxin and killed cholera vibrios, has been shown to provide effective protection against cholera for at least 3 years without any side effects, based on extensive clinical trials.

This vaccine also offers some protection against diarrhea caused by enterotoxinogenic E. coli (ETEC), and advancements in recombinant DNA techniques suggest that a new effective oral ETEC vaccine may soon be developed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of oral vaccines against cholera and enterotoxinogenic Escherichia coli diarrhea. Holmgren, J., Svennerholm, AM.[2006]

The live attenuated vaccine CVD103-HgR has shown effectiveness after just one dose, although it may cause mild diarrhea in about 4% of recipients, indicating a generally favorable safety profile.

The killed whole cell vaccine combined with the cholera enterotoxin B subunit is safe but requires multiple doses, highlighting the trade-off between safety and convenience in vaccine administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vibrio cholerae vaccines. Kaper, JB.[2019]

References

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

Vaxchora: A Single-Dose Oral Cholera Vaccine. [2018]

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

Vaxchora: The First FDA-Approved Cholera Vaccination in the United States. [2020]

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

An overview of VaxchoraTM, a live attenuated oral cholera vaccine. [2023]

4. England pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

New vaccines against bacterial enteric infections. [2005]

6. England pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

Development of oral vaccines against cholera and enterotoxinogenic Escherichia coli diarrhea. [2006]

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

Vibrio cholerae vaccines. [2019]