Hookworm Vaccine for Hookworm Infection

Overseen By Study Coordinator

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Pregnancy, Immunodeficiency, Severe asthma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

35 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you have used corticosteroids (except topical or nasal) or immunosuppressive drugs within 30 days before the study or plan to use them during the study.

What data supports the effectiveness of the hookworm larvae treatment for hookworm infection?

Research on hookworm vaccines shows that targeting specific proteins in the hookworm can protect against infection, as seen in animal studies. Additionally, vaccines using similar components have been safe and well-tolerated in early human trials, suggesting potential effectiveness. ^{1 2 3 4 5}

How is the hookworm vaccine treatment different from other treatments for hookworm infection?

The hookworm vaccine treatment is unique because it aims to prevent infection by targeting specific proteins in the hookworm's digestive system, unlike current treatments that rely on drugs to kill the worms after infection. This vaccine approach could reduce the cycle of reinfection and drug resistance seen with existing treatments. ^{1 2 3 4 5}

What is the purpose of this trial?

An experimental hookworm infection model is being developed to provide early proof-of-concept that a hookworm vaccine targeting the blood-feeding pathway of adult hookworms is feasible and efficacious. The proposed model consists of vaccinating healthy, hookworm-naïve adults with a candidate hookworm vaccine, followed by challenging them with the investigational product, Necator americanus Larval Inoculum to assess the effect of vaccination on infection. The first proposed study will be a feasibility study that will consist of administering different doses of the Necator americanus Larval Inoculum to healthy adult volunteers to determine the optimal dose (i.e., number of infectious larvae) that is safe, well-tolerated and results in consistent infection.

Research Team

David J Diemert, MD

Principal Investigator

George Washington University

Eligibility Criteria

Healthy adults aged 18-45 who have never had a hookworm infection can join this trial. They must be in good health, not pregnant or breastfeeding, willing to use contraception if applicable, and available for the next 6 months. People with significant health issues like heart or liver disease, immunodeficiency, certain blood conditions, severe allergies or asthma cannot participate.

Inclusion Criteria

Good general health as determined by means of the screening procedure

Willingness to participate in the study as evidenced by signing the informed consent document

Available for the duration of the trial (6 months)

Exclusion Criteria

Laboratory evidence of liver disease (alanine aminotransferase [ALT] greater than 1.25-times the upper reference limit)

Laboratory evidence of hematologic disease (hemoglobin <11.5 g/dl [females] or <12.5 g/dl [males]; absolute leukocyte count <3.6 or >10.7 x 103/mm3; absolute neutrophil count [ANC] <1.7 x 103/mm3; absolute lymphocyte count <0.7 x 103/mm3; or platelet count <140 x 103/mm3)

History of hypoalbuminemia

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single application of Necator americanus Larval Inoculum on Study Day 0, with doses of 25, 50, or 75 larvae depending on cohort

1 day

1 visit (in-person)

Observation and Safety Assessment

Participants are monitored for safety and tolerability, with capsule endoscopy performed between Study Day 70 and 77 for up to 5 volunteers per cohort

3 months

Multiple visits (in-person)

Anthelmintic Treatment

Participants receive a 3-dose treatment of albendazole (400 mg per dose) for clearance of experimental infection

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Treatment Details

Interventions

• Necator americanus Hookworm Larvae

Trial Overview The study is testing whether a vaccine against hookworms is effective by giving healthy volunteers the vaccine and then exposing them to Necator americanus larvae. The goal is to find a safe dose of larvae that consistently causes infection without serious side effects.

Participant Groups

Group I: Cohort 3 (75 Necator americanus Hookworm Larvae) Experimental Treatment 1 Intervention

A dose of 75 Necator americanus Hookworm Larvae, administered via a sterile absorbent pad fixed with a transparent adhesive dressing for at least 1 hour.

Group II: Cohort 2 (50 Necator americanus Hookworm Larvae) Experimental Treatment 1 Intervention

A dose of 50 Necator americanus Hookworm Larvae, administered via a sterile absorbent pad fixed with a transparent adhesive dressing for at least 1 hour.

Group III: Cohort 1 (25 Necator americanus Hookworm Larvae) Experimental Treatment 1 Intervention

A dose of 25 Necator americanus Hookworm Larvae, administered via a sterile absorbent pad fixed with a transparent adhesive dressing for at least 1 hour.

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Findings from Research

A novel lipopeptide oral vaccine targeting the hookworm Necator americanus was developed, which successfully generated a strong immune response in mice against the parasite.

In a rodent model, this vaccine led to remarkable protection, reducing intestinal worm and egg burdens by up to 98% and 99%, respectively, demonstrating its potential efficacy as a preventive measure against hookworm infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipopeptide-Based Oral Vaccine Against Hookworm Infection. Bartlett, S., Eichenberger, RM., Nevagi, RJ., et al.[2020]

Human hookworms, particularly Necator americanus and Ancylostoma duodenale, infect approximately 1 billion people, primarily in rural poverty areas, highlighting the urgent need for effective vaccines.

Progress has been made in developing recombinant vaccines against hookworm, but challenges remain due to the complex immune response and the nature of the infection, necessitating a targeted approach for vaccine development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A history of hookworm vaccine development. Schneider, B., Jariwala, AR., Periago, MV., et al.[2021]

Hookworm infections, caused by Necator americanus and Ancylostoma duodenale, lead to significant health issues like chronic anemia and protein malnutrition, highlighting the need for new control strategies beyond current mass drug administration.

Progress is being made in developing a vaccine against hookworm infection, specifically the N. americanus Ancylostoma Secreted Protein-2 vaccine, with plans to create a combination vaccine targeting both larval and adult stages of the hookworm life cycle.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hookworm vaccines. Diemert, DJ., Bethony, JM., Hotez, PJ.[2008]

The study identified rAceyCP1 as a promising vaccine candidate against the A. ceylanicum hookworm, showing that it can significantly reduce hookworm burdens and fecal egg counts in vaccinated hamsters, indicating its potential efficacy.

Vaccination with rAceyCP1 led to a strong immune response, as evidenced by high serum IgG levels and specific Th2 immune responses, suggesting that this vaccine could be a viable option for preventing hookworm infections in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A highly expressed intestinal cysteine protease of Ancylostoma ceylanicum protects vaccinated hamsters from hookworm infection. Noon, JB., Schwarz, EM., Ostroff, GR., et al.[2023]

The co-administered Na-GST-1 and Na-APR-1 vaccines were found to be safe and well tolerated in a phase 1 trial involving 32 healthy adults in Gabon, with no severe adverse events reported.

Vaccination induced significant IgG antibody responses to both antigens, particularly at the 100 μg dose, indicating promising immunogenicity that supports further development of these vaccines for hookworm prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of co-administered hookworm vaccine candidates Na-GST-1 and Na-APR-1 in Gabonese adults: a randomised, controlled, double-blind, phase 1 dose-escalation trial. Adegnika, AA., de Vries, SG., Zinsou, FJ., et al.[2021]

References

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

Lipopeptide-Based Oral Vaccine Against Hookworm Infection. [2020]

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

A history of hookworm vaccine development. [2021]

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

Hookworm vaccines. [2008]

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

A highly expressed intestinal cysteine protease of Ancylostoma ceylanicum protects vaccinated hamsters from hookworm infection. [2023]

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

Safety and immunogenicity of co-administered hookworm vaccine candidates Na-GST-1 and Na-APR-1 in Gabonese adults: a randomised, controlled, double-blind, phase 1 dose-escalation trial. [2021]