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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how typhoid and cholera vaccines affect the immune system and gut bacteria. Participants will be divided into three groups: one group receives a vaccine before a routine endoscopy, another receives a vaccine after an initial endoscopy, and the last group undergoes an endoscopy without vaccination. Volunteers must already be scheduled for an endoscopy at the University of Maryland Medical Center and be in good health as determined by their healthcare provider. As a Phase 4 trial, this research focuses on understanding how these FDA-approved vaccines can benefit 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 on medications that cause immunosuppression, you may not be eligible to participate.

What is the safety track record for these treatments?

Research has shown that both Vaxchora and Vivotif are safe for use. Vaxchora, a drinkable vaccine for cholera, has been tested in over 3,000 adults. Most participants experienced only mild side effects, such as fatigue or headache. The FDA has approved it, indicating it has passed strict safety tests.

Vivotif, a drinkable vaccine for typhoid, is also FDA-approved. Safety studies found no serious side effects, even with up to eight doses. Some individuals may experience mild symptoms like stomach pain.

Both vaccines are "live attenuated," containing a weakened form of the virus or bacteria. This helps the body build protection without causing illness. Overall, these vaccines are well-tolerated and have a strong safety record among adults. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these vaccines because Vivotif and Vaxchora target typhoid and cholera, offering an innovative approach to understanding immune responses at the gut level. Unlike standard oral vaccines, this trial involves collecting specimens before and after vaccination through endoscopy, allowing scientists to observe changes directly in the small intestine's mucosal environment. This provides a unique opportunity to assess how these vaccines influence gut microbiota and immune responses, potentially leading to more effective immunization strategies.

What evidence suggests that this trial's vaccines could be effective for typhoid and cholera?

Research has shown that Vaxchora, the oral cholera vaccine, strengthens the immune system by increasing certain proteins in the blood that combat cholera bacteria. This protection can last for at least two years in teenagers. Vivotif, the oral typhoid vaccine, effectively boosts the body's defenses against the bacteria causing typhoid fever. In this trial, some participants will receive immunization with Vivotif and/or Vaxchora before or between endoscopic examinations to assess immune responses. Both vaccines have FDA approval and are used to protect travelers from these diseases. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

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

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

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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, 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]

Citations

1. vaxchora.com vaxchora.com/

Vaxchora® Oral Cholera Vaccine (Live) In these studies, immune response to VAXCHORA was based on seroconversion. A vibriocidal antibody assay was used to measure serum levels of neutralizing ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8103473/

Long-Term Immunogenicity of Live Oral Cholera Vaccine ... Vaccination with PXVX0200 produces an immune response which persists for at least 2 years in adolescents aged 12–17 years.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36959054/

Immunogenicity of partial doses of live oral cholera vaccine ... Vaccination with PXVX0200 produced an immune response in most children who received partial dosing. Since SVA seroconversion is a strong ...

4. fda.gov fda.gov/media/128415/download

Package Insert - VAXCHORA The immunologic response to VAXCHORA may be diminished in immunocompromised individuals [see Drug Interactions (7.3)]. 11 DESCRIPTION. VAXCHORA (Cholera Vaccine ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03251495

Immunologic Responses to a Live Attenuated Oral Cholera ... The primary objective of this study is to evaluate the antibody response to the cholera vaccine, Vaxchora®, in healthy subjects.

6. medicomart.com medicomart.com/images/document/MSDS_Vaxchora_BN.pdf

Material Safety Data Sheet Vaxchora (Cholera Vaccine, Live, Oral) is approved by the US Food and Drug Administration for human use as well as the European Medicines Agency. 16. Other ...

7. ec.europa.eu ec.europa.eu/health/documents/community-register/2021/20210226150974/anx_150974_en.pdf

Vaxchora, Cholera vaccine (recombinant, live, oral) The safety and efficacy of Vaxchora in children less than 2 years has not been established. No data are available. Page 3. 3. Method of administration.

8. vaxchora.com vaxchora.com/consumer/

Consumer & Patient Information | Vaxchora® Oral Cholera ... Use and Important Safety Information for VAXCHORA® (vaks-CORE-ah). It is also known as Cholera Vaccine, Live, Oral. · What is VAXCHORA used for? · Who should not ...