The global health challenge of hookworm infection, a soil-transmitted helminthic disease, is by far the most scary especially in tropical and subtropical countries. At Protheragen, we are committed to advancing the fight against hookworm infection through our comprehensive suite of drug and therapy research services.
Introduction to Hookworm Infection
Hookworm infection is a life-threatening parasitic disease transmitted by helminth parasites living in the intestines of human beings. The most frequently infecting species are Necator americanus and Ancylostoma duodenale, and their combined worldwide prevalence is about 438.9 million.
These parasitic worms that live in the intestines of a person feed on the blood leading to an Iron Deficiency Anemia which is one of the common causes of morbidity, especially in children and women of reproductive age from developing tropical regions. Studies have shown that physical and mental development is inhibited in populations where Hookworm infection is prevalent, which presents a huge public health and economic problem.
Fig.1 Life cycle of Necator americanus. (Loukas A., et al., 2016)
Vaccine Development for Hookworm Infection
The creation of a vaccine against hookworms entails the selection of antigens that can stimulate an adequate immune response. Two recombinant antigens that appear to have prospective promise in early trials are:
- Na-APR-1 (Necator americanus aspartic protease-hemoglobinase): This antigencleaves hemoglobin which is vital for the sustenance of hookworms. The aim of vaccines based on Na-APR-1 is to target and destroy all aspartic proteases in the worm so that the parasites can no longer survive within their hosts.
- Na-GST-1 (Necator americanus glutathione-S-transferase): This antigen participates in the detoxification of heme which is an end product of hemoglobin's proteolytic degradation. Na-GST-1 vaccines are also designed to combat an organism's attempt to detoxify so that the parasites can further be destroyed.
Table 1. Overview of vaccine candidate. (Puchner K. P., et al., 2024)
| Candidate |
Developer/manufacturer |
Antigen platform |
Phase of development, population, and location |
Route of administration, no. of doses, schedule |
Presentation and stability |
| Combined rNa-GST-1 + rNa-APR-1 with Alhydrogel, GLA or CpG |
Texas Children's Center for Vaccine Development |
Both expression systems |
Phase 1 |
I.M. 3 doses |
Available from the Texas Children's Center for Vaccine Development |
| rNa-APR-1/A with Alhydrogel, GLA or CpG |
Texas Children's Center for Vaccine Development with Fraunhofer |
Expression system tobacco plants |
Phase 1 |
I.M. 3 doses |
Available from the Texas Children's Center for Vaccine Development |
| rNa-GST-1/Alhydrogel vaccine with Alhydrogel, GLA or CpG |
Texas Children's Center for Vaccine Development with Aeras and Walter Reed Army Institute of Research |
Expression system Pichia pastoris |
Phase 1–2 |
i.m. |
Available from the Texas Children's Center for Vaccine Development |
| 3 dosages |
| rNA-ASP-2 |
Previously Walter Reed Army Institute of Research and Instituto Butantan |
Pichia pastoris |
Discontinued following phase 1 studies |
I.M. 3 doses |
Available from the Texas Children's Center for Vaccine Development |
Therapeutics Development for Hookworm Infection
- Benzimidazole-Based Therapies
Albendazole and mebendazole stand at the forefront of hookworm therapeutic drugs by inhibiting microtubule polymerization in helminths. Their efficacy, however, remains an issue either by its varied effectiveness or the likelihood of the drug resistance. For example, a single dose therapy of albendazole at 400 mg demonstrated cure rate up to 72 percent, whereas mebendazole showed very low cure rate.
- Alternative Therapies
Tribendimidine: This chemical derivative of amidantel was shown to be very active against hookworms in animal and human trials, and may have some utility as an alternative to benzimidazoles.
Combination Therapies: The application of multiple pharmacological agents, with distinct targets and mechanisms of action, could bring about better therapeutic results and postpone the evolution of resistance. For instance, combinations of albendazole with oxantel pamoate or ivermectin has been tried but not always with positive outcomes.
Our Services
As a research service provider, Protheragen is at the forefront of advancing hookworm infection vaccine and therapeutics development services. Our comprehensive approach includes:
Preclinical Research
- Pharmacodynamics Study Services
- Pharmacokinetics Study Services
- Drug Safety Evaluation Services
Disease Models
- Hookworm Infection Dog Models: Infections in dogs lead to anemia and eosinophilia, similar to human hookworm infections.
- Hookworm Infection Hamster Models: This model reproduces weight and blood loss similar to human
In addition, we also provide the following optional services:
- Immunological Assessments: Utilizing cutting-edge technologies, we evaluate the immunogenicity of vaccine candidates and the efficacy of therapeutic agents in relevant animal models.
- Molecular Biology and Genomics: Our team of experts applies genomics to identify key antigenic and molecular targets for vaccine and drug development, facilitating precision approaches to helminth control.
- Pharmacokinetic and Pharmacodynamic Studies: Protheragen conducts detailed pharmacological assessments to optimize dosing regimens and predict therapeutic outcomes in human populations.
If you are interested in our services, please feel free to contact us.
References
- Loukas, Alex, et al. "Hookworm infection." Nature reviews Disease primers 2.1 (2016): 1-18.
- Haldeman, Matthew S., Melissa S. Nolan, and Kija RN Ng'habi. "Human hookworm infection: is effective control possible? A review of hookworm control efforts and future directions." Acta tropica 201 (2020): 105214.
- Puchner, Karl Philipp, et al. "Vaccine value profile for Hookworm." vaccine 42.19 (2024): S25-S41.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
