Vaccine for E. coli Infections

Recruiting at 1 trial location

Overseen By Robert W. Frenck

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Antibiotics, Corticosteroids, Antipsychotics, others

Disqualifiers: IBD, HIV, Neoplastic disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

72 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new vaccine, CssBA+dmLT, designed to protect against E. coli infections that cause moderate to severe diarrhea. Researchers aim to evaluate the vaccine's safety and effectiveness in preventing these infections. Participants will receive either the vaccine or a placebo and will later be exposed to a strain of E. coli to assess the vaccine's effectiveness. The trial seeks healthy adults who can adhere to the study's procedures and have not recently experienced E. coli infections or serious gastrointestinal issues. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify that you must stop taking your current medications. However, any changes in medication should not be due to a worsening condition, and certain medications like systemic antibiotics and some over-the-counter drugs should not be taken close to the vaccination dates. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that the vaccine CssBA, combined with dmLT, has undergone safety testing as an injection. In earlier studies, most participants tolerated the vaccine well, experiencing only mild reactions like soreness at the injection site. Serious side effects were rare and not directly linked to the vaccine.

This trial is in an early stage, indicating some evidence of safety, but further research is necessary. The vaccine targets a specific part of the E. coli bacteria to help prevent moderate to severe diarrhea. Overall, the evidence so far suggests it is safe for people, but more data is needed for confirmation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the CssBA+dmLT vaccine for E. coli infections because it offers a novel approach to preventing infections caused by the ETEC strain. Unlike traditional treatments, which typically involve antibiotics to manage symptoms after infection, this vaccine aims to prevent the infection entirely by using a combination of the CssBA protein and dmLT adjuvant to stimulate the immune system. This proactive strategy could reduce the reliance on antibiotics and help manage antibiotic resistance. Additionally, the vaccine is administered through a simple intramuscular injection, making it potentially more accessible and easier to distribute on a large scale.

What evidence suggests that this vaccine might be an effective treatment for E. coli infections?

Research shows that the CssBA+dmLT vaccine, which participants in this trial may receive, could help fight E. coli infections. Previous studies have found that this vaccine is safe and can trigger an immune response, indicating potential effectiveness against the bacteria. In animal studies, E. coli vaccines have greatly reduced infections, suggesting similar results might occur in humans. The vaccine aims to prevent moderate to severe diarrhea by targeting specific parts of the bacteria, making it harder for the bacteria to cause illness. While more information from human trials is needed, these early results offer hope for effective protection against E. coli. ^{2 5 6 7 8}

Are You a Good Fit for This Trial?

Healthy adults aged 18-49, not pregnant or breastfeeding, with a BMI of 19 to <40 kg/m^2. Participants must be willing to follow the study procedures and use effective contraception if applicable. They should have stable chronic health conditions and no acute illnesses that could affect the trial's outcomes.

Inclusion Criteria

My BMI is between 19 and 40.

My temperature is below 100.4°F (38°C) at enrollment.

I am willing and able to give my consent for the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination

Participants receive 3 intramuscular doses of vaccine or placebo at 3-week intervals

6 weeks

3 visits (in-person)

Challenge and Treatment

Participants meeting challenge criteria are admitted to an inpatient unit, receive an oral dose of ETEC, and are treated with antibiotics after 5 days

5-8 days

Inpatient stay

Follow-up

Participants are monitored for safety and immunologic parameters after discharge, with outpatient visits and a phone visit

4 weeks

5 visits (in-person), 1 visit (phone)

What Are the Treatments Tested in This Trial?

Interventions

• CssBA+dmLT

Trial Overview The trial is testing a CS6 based vaccine (CssBA) combined with double mutant labile toxin (dmLT) against ETEC strain B7A-induced moderate-severe diarrhea in healthy adults. Participants will receive three IM doses of either the vaccine or placebo before being exposed to ETEC for efficacy evaluation.

How Is the Trial Designed?

Group I: Cohort 2A Experimental Treatment 3 Interventions

Participants will receive 45 mcg CssBA with 0.5 mcg dmLT vaccine intramuscular injection on Days 1, 22 and 43, outpatient. Participants who meet the challenge criteria will orally receive 1x10\^10 cfu of ETEC strain B7A, inpatient, approximately 28 days after the third dose of study agent. N= 18.

Group II: Cohort 1A Experimental Treatment 3 Interventions

Participants will receive 45 mcg CssBA with 0.5 mcg dmLT vaccine intramuscular injection on Days 1, 22 and 43, outpatient. Participants who meet challenge criteria will orally receive 1x10\^10 cfu of ETEC strain B7A, inpatient, approximately 28 days after the third dose of study agent. N= 18.

Group III: Cohort 2B Placebo Group 2 Interventions

Participants will receive 0.6 mL of 0.9% normal saline intramuscular injection on Days 1, 22 and 43, outpatient. Participants who meet the challenge criteria will orally receive 1x10\^10 cfu of ETEC strain B7A, inpatient, approximately 28 days after the third dose of study agent. N= 18.

Group IV: Cohort 1B Placebo Group 2 Interventions

Participants will receive 0.6 mL of 0.9% normal saline intramuscular injection on Days 1, 22 and 43, outpatient. Participants who meet challenge criteria will orally receive 1x10\^10 cfu of ETEC strain B7A, inpatient, approximately 28 days after the third dose of study agent . N= 18.

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

Both live-attenuated and inactivated APEC vaccines provided significant protection against APEC infections in turkeys, indicating their efficacy in preventing acute colibacillosis.

The study found that Th2-biased immune responses were primarily induced by the vaccines, and using Th2-biasing adjuvants enhanced protection, suggesting that both antibody and cell-mediated responses are crucial for effective vaccination against APEC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune responses associated with homologous protection conferred by commercial vaccines for control of avian pathogenic Escherichia coli in turkeys. Sadeyen, JR., Wu, Z., Davies, H., et al.[2018]

The BamA protein from pathogenic E. coli shows high sequence conservation and low allergenicity, making it a promising candidate for a universal vaccine against colibacillosis and related infections from Salmonella and Shigella.

Immunization with the BamA protein significantly increased survival rates in mice (80% survival compared to 20% in the control group), and enhanced the phagocytic activity of neutrophils against E. coli, indicating its potential efficacy as a protective vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In silico analysis and recombinant expression of BamA protein as a universal vaccine against Escherichia coli in mice. Guan, Q., Wang, X., Wang, X., et al.[2017]

The double-mutant heat-labile toxin (dmLT) significantly enhances antibody responses to all seven antigens in the ETEC adhesin-based vaccine when administered subcutaneously, demonstrating its effectiveness as a parenteral adjuvant.

The optimal dose of dmLT for enhancing immune response was found to be 0.1 µg, indicating that even low doses can effectively boost the efficacy of vaccines, which could be beneficial for developing vaccines against ETEC and potentially other pathogens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant effect of enterotoxigenic Escherichia coli (ETEC) double-mutant heat-labile toxin (dmLT) on systemic immunogenicity induced by the CFA/I/II/IV MEFA ETEC vaccine: Dose-related enhancement of antibody responses to seven ETEC adhesins (CFA/I, CS1-CS6). Seo, H., Lu, T., Mani, S., et al.[2021]

Intramuscular vaccination with bacterial ghosts from Escherichia coli CE9 in mice generated a stronger immune response, including higher levels of IgG and IgA antibodies, compared to subcutaneous and oral routes, indicating its potential as an effective prophylactic strategy against colibacillosis.

The intramuscular route not only improved antibody production but also resulted in better survival rates and less tissue damage in vital organs compared to traditional inactivated vaccines and the oral route, highlighting its efficacy in preventing E. coli infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative study of subcutaneous, intramuscular, and oral administration of bovine pathogenic Escherichia coli bacterial ghost vaccine in mice. Mu, J., Lei, L., Zheng, Y., et al.[2022]

The ∆aroA mutant strain of avian pathogenic E. coli was found to be safe for vaccination in chicks, as it did not cause mortality, lesions, or weight loss after administration.

However, the vaccine did not provide significant protection against colibacillosis challenges, likely due to factors like high maternal antibody levels and the vaccination method used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of immunity against avian colibacillosis induced by an aroA mutant containing increased serum survival gene in broilers. Salehi, TZ., Tabatabaei, S., Karimi, V., et al.[2021]

The K88ac-3STa-LTB vaccine effectively neutralizes the STa toxin and stimulates strong immune responses, achieving an 85% protection rate in newborn piglets shortly after suckling, indicating its potential efficacy against E. coli diarrhea.

The vaccine was shown to be safe, as it lost the toxicity of the natural STa enterotoxin, and the minimum immunization doses were established at 0.2 mL for mice and 2.5 mL for pregnant sows, ensuring appropriate dosing for effective immunization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preparation of novel trivalent vaccine against enterotoxigenic Escherichia coli for preventing newborn piglet diarrhea. Xu, C., Peng, K., She, Y., et al.[2023]

Hyperantigenic preparations of synthetic Escherichia coli heat-stable toxin (ST) can create more effective vaccines, showing nearly 10-fold less toxicity compared to traditional ST vaccines while maintaining similar immunogenicity.

Vaccines containing hyperantigenic ST preparations led to significant increases in protective mucosal immunoglobulin A antitoxin levels in rats, indicating enhanced immune response and protection against bacterial challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Properties of cross-linked toxoid vaccines made with hyperantigenic forms of synthetic Escherichia coli heat-stable toxin. Klipstein, FA., Engert, RF., Houghten, RA.[2021]

A multi-strain vaccine containing heat-killed uropathogenic bacteria significantly reduced bladder infections in cynomolgus monkeys after being administered either vaginally or intramuscularly following induced E. coli cystitis.

The vaccine demonstrated efficacy against cystitis in both nonhuman primates and humans, suggesting its potential as a viable treatment option for urinary tract infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaginal immunization of monkeys against urinary tract infection with a multi-strain vaccine. Uehling, DT., Hopkins, WJ., James, LJ., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06692907?term=AREA%5BBasicSearch%5D(cs6)&rank=6&checkSpell=

Efficacy Study of IM Administered CssBA+dmLT Against ... The study is designed to evaluate the safety, immunogenicity, and efficacy of the intramuscular administration of a CS6 based vaccine (CssBA) against ETEC co- ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34419306/

Safety and immunogenicity of intramuscularly administered ... This is the first study to demonstrate the safety and immunogenicity of CssBA and/or dmLT administered intramuscularly.

3. withpower.com withpower.com/trial/vaccine-for-e-coli-infections-2efec

Vaccine for E. coli Infections The research on a multi-strain vaccine containing E. coli strains showed that it significantly reduced bladder infections in monkeys, suggesting potential ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0264410X23001378

Vaccine value profile for enterotoxigenic Escherichia coli ... A safe, effective, and affordable ETEC vaccine that reduces mortality and morbidity due to moderate-to-severe diarrhoeal disease in infants and children under ...

5. journals.asm.org journals.asm.org/doi/pdf/10.1128/iai.00368-25?download=true

Recent progress in enterotoxigenic Escherichia coli ... Whether anti-LT immunity derived from dmLT can effectively protect against LT +. ETEC infections is yet to be demonstrated. A vaccine candidate ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8461560/

Safety and immunogenicity of intramuscularly administered ... We assessed the safety and immunogenicity of a CS6-targeted candidate vaccine, CssBA, co-administered intramuscularly with the double-mutant heat-labile ...

7. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/556275

Efficacy Study of IM Administered CssBA+dmLT Against ... The study is designed to evaluate the safety, immunogenicity, and efficacy of the intramuscular administration of a CS6 based vaccine (CssBA) against ETEC ...

8. idcrc.org idcrc.org/about/news-archive/etec.html

IDCRC launches clinical trial to evaluate vaccine aimed at ... This Phase 2b trial is designed to evaluate the safety, immunogenicity, and efficacy of the intramuscular administration of a CS6 based vaccine ...