# Controlled Infection Trial to Test Efficacy of Hookworm Vaccine with Different TLR Agonists

> **NIH NIH U01** · GEORGE WASHINGTON UNIVERSITY · 2022 · $480,908

## Abstract

Project Summary/Abstract
This U01 grant proposal will utilize a novel paradigm for the early assessment of vaccine efficacy and the
selection of optimal vaccine formulation. We will conduct a Phase 2 clinical trial that enables the evaluation of
an investigation hookworm vaccine by challenging human volunteers with a controlled human hookworm
infection (CHHI) after vaccination. Hookworm is one of the most important parasitic infections, with over 500
million people infected worldwide, most with Necator americanus. The clinical hallmark of hookworm infection
is iron deficiency anemia, resulting from intestinal blood loss directly caused by this parasite. Glutathione-S-
Transferase-1 of N. americanus (Na-GST-1) is a component of the blood-feeding pathway of this intestinal
helminth and was selected for clinical development based on its protective effect in animal studies.
Recombinant Na-GST-1 formulated on Alhydrogel® has been shown to be safe when administered to healthy
adults in Phase 1 trials in the USA and in hookworm endemic areas of Brazil and Gabon. In the proposed
Phase 2 study, healthy hookworm‐naïve adult volunteers will be vaccinated with Na-GST-1/Alhydrogel®
followed by challenging them with infective N. americanus larvae to determine the effect of vaccination on
hookworm infection by parasitologic, hematologic, and immunologic parameters.
Traditionally, proof-of-concept studies for investigational vaccines are conducted later in clinical development
and usually in large field trials in pathogen endemic areas. These studies can take considerable time and
involve large numbers of participants, depending on the incidence of the infection. The objective of this U01
proposal is to conduct a Phase 2 clinical trial in which proof-of-concept for this new vaccine for hookworm is
tested early in clinical development and on a small number of volunteers. In addition, we will utilize state-of-
the-art immunological technologies to comprehensively evaluate the humoral and cellular immune response to
vaccination and how that translates into protection in the CHHI model. Hence, the proposed clinical trial will
also serve to optimize the component combinations of the final vaccine formulation, especially the addition of
novel Toll-Like Receptor immunostimulants such as GLA-AF and CpG. The results of this trial will permit
critical decisions to be made on the further development of the Na-GST-1 hookworm vaccine and its final
formulation, prior to conducting larger, more costly Phase 2 and 3 trials in hookworm endemic areas.

## Key facts

- **NIH application ID:** 10556618
- **Project number:** 4U01AI129789-05
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** Jeffrey Michael Bethony
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $480,908
- **Award type:** 4C
- **Project period:** 2017-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10556618

## Citation

> US National Institutes of Health, RePORTER application 10556618, Controlled Infection Trial to Test Efficacy of Hookworm Vaccine with Different TLR Agonists (4U01AI129789-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10556618. Licensed CC0.

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