Hookworm infection, a soil-transmitted helminthic disease, poses a significant global health challenge, particularly in tropical and subtropical regions. 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 serious parasitic disease caused by soil-transmitted nematode parasites that reside in the human intestine. The predominant infecting species are Necator americanus and Ancylostoma duodenale, which together affect an estimated 438.9 million people globally.
These parasitic worms feed on the blood of their human hosts, leading to iron-deficiency anemia - a major cause of morbidity, especially in children and women of childbearing age living in developing tropical regions. Hookworm infection has been shown to impair both physical and cognitive development in affected populations, posing a substantial public health and economic burden.
Fig.1 Life cycle of Necator americanus. (Loukas A., et al., 2016)
Vaccine Development for Hookworm Infection
The development of a hookworm vaccine involves targeting specific antigens that can elicit a protective immune response. Two leading recombinant antigens showing promise in early trials are:
- Na-APR-1 (Necator americanus aspartic protease-hemoglobinase): This antigen aids in the digestion of hemoglobin, a crucial process for the survival of hookworms. Vaccines targeting Na-APR-1 aim to disrupt this essential function, thereby limiting the parasite's ability to sustain itself within the host.
- Na-GST-1 (Necator americanus glutathione-S-transferase): This antigen is involved in the detoxification of heme, a byproduct of hemoglobin digestion. Na-GST-1 vaccines seek to neutralize this detoxification process, further impairing the hookworm's survival mechanisms.
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 are the cornerstone of current hookworm therapeutics, acting by inhibiting microtubule polymerization in helminths. However, their efficacy varies, and there are concerns about the development of drug resistance. For instance, a single dose of albendazole has shown a cure rate of up to 72%, while mebendazole has a significantly lower cure rate.
- Alternative Therapies
Tribendimidine: This synthetic derivative of amidantel has demonstrated high activity against hookworms in both animal models and human studies, offering a potential alternative to benzimidazoles.
Combination Therapies: The use of drugs with different mechanisms of action may improve therapeutics efficacy and delay the emergence of resistance. For example, combinations of albendazole with oxantel pamoate or ivermectin have been explored, although with mixed results.
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.
