Hookworm Vaccine for Hookworm Infection

Recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a potential vaccine for hookworm infections by determining if it can prevent the worms from feeding on blood. Participants will receive varying doses of Necator americanus hookworm larvae to identify the safest and most effective amount for causing a consistent infection. Healthy adults who have never had a hookworm infection and have not lived in areas where hookworms are common may qualify for this study. The goal is to assess whether this vaccine can help prevent hookworm infection in the future. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new vaccine.

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.

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

Research shows that Necator americanus, the hookworm used in this trial, commonly causes hookworm infections worldwide, particularly in rural areas with poverty. Although widespread, these infections are usually not life-threatening.

Previous studies have found that short-term exposure to these larvae can cause a skin reaction and an increase in certain white blood cells called eosinophils. These effects indicate an immune response but typically do not lead to serious health problems. The goal is to find a dose that is both safe and effective for study purposes.

As this trial is in an early stage, the main aim is to determine if the doses are safe and well-tolerated. While this specific trial may not yet have extensive safety data, researchers conduct studies with Necator americanus using careful risk management. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for hookworm infection, which usually involve antiparasitic drugs like albendazole or mebendazole, this new approach uses live Necator americanus hookworm larvae. Researchers are excited because these larvae may help the body build immunity against hookworms in a more natural and potentially longer-lasting way. The treatment involves administering the larvae via a simple absorbent pad, which is a novel and less invasive delivery method compared to traditional oral medications. This method could offer a new way to prevent hookworm infection rather than just treating it after the fact.

What evidence suggests that this trial's treatments could be effective for hookworm infection?

This trial will evaluate different doses of Necator americanus hookworm larvae as a potential vaccine for hookworm infection. Research has shown that short-term exposure to Necator americanus hookworm larvae can help protect the body. Studies have found that this type of hookworm infection is generally safe, with no deaths reported among over 500 participants in similar studies. Hookworm infection is a major health problem, affecting about 500 million people worldwide, mostly in low-income countries. It mainly causes issues like anemia (when the body doesn't have enough healthy red blood cells) and malnutrition. The goal of using hookworm larvae in a vaccine is to lessen these problems by targeting the worms' blood-feeding habits. Early research suggests this method is promising. ^{5 6 7 8 9}

Who Is on the Research Team?

David J Diemert, MD

Principal Investigator

George Washington University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

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sciencedirect.com

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Protective efficacy of short-term infection with Necator ...

This is the first study to describe a protective effect of short-term exposure to hookworm larvae and show an association with skin response, eosinophilic ...

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pmc.ncbi.nlm.nih.gov

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Experimental human hookworm infection: a narrative historical ...

Experimental human hookworm infection has been proven to be safe, with no deaths observed in over 500 participants.

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Modeling the Economic and Epidemiologic Impact ...

Human hookworm infection is a major cause of anemia and malnutrition, affecting almost 500 million people in low- and middle-income countries[1]. Unlike other ...

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sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0882401025003171

Accelerating human hookworm vaccine development

The new world hookworm, Necator americanus, caused most hookworm infections (80 %), with much of the current transmission occurring among individuals living in ...

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Hookworm infection | Nature Reviews Disease Primers

Alternative and newer estimates indicate that hookworm infection results in 4.1 million DALYs lost, as well as possibly over US$100 billion in ...

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Necator americanus - Pathogen Safety Data Sheets

PHYSICAL INACTIVATION: N. americanus larvae are susceptible to desiccation and freezing 15. They have lower survival times and physical resistance outside the ...

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ncbi.nlm.nih.gov

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Hookworm - StatPearls - NCBI Bookshelf - NIH

Necator americanus is the major cause of hookworm infections worldwide, while Ancylostoma duodenale tends to be endemic to the Mediterranean region and ...

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emedicine.medscape.com

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Hookworm Disease: Background, Pathophysiology, Etiology

Human hookworm disease is a common helminth infection worldwide that is predominantly caused by the nematode parasites Necator americanus and Ancylostoma ...

9.

nejm.org

nejm.org/doi/full/10.1056/NEJMra032492

Hookworm Infection

It is one of the most common chronic infections, with an estimated 740 million cases in areas of rural poverty in the tropics and subtropics.