African trypanosomiasis, commonly referred to as sleeping sickness, is an infectious condition triggered by a protozoan parasite from the genus Trypanosoma, specifically the species brucei. The disease is transmitted through the bites of tsetse flies, which belong to the genus Glossina. As a prominent company, we are focus on developing vaccines and therapies for African trypanosomiasis, providing high-quality services to support your research.
Overview of African Trypanosomiasis
African trypanosomiasis, also known as sleeping sickness, is a parasitic disease caused by Trypanosoma species transmitted by tsetse flies. According to recent literature, the disease primarily affects rural populations in sub-Saharan Africa, with an estimated 70 million people at risk. The World Health Organization reported that in 2023, there were approximately 1,500 new cases, reflecting a significant decrease in incidence due to ongoing control measures.
Fig.1 Geographical distribution of reported infections of human African trypanosomiasis. (Pérez-Molina JA and Molina I., 2018)
Pathogenesis of African Trypanosomiasis
The pathogenesis of African trypanosomiasis involves an acute phase characterized by a high parasitic load and mild symptoms, followed by a chronic phase where the parasite persists in tissues, particularly the heart. In the hemolymphatic stage, parasites multiply in the bloodstream, causing symptoms like fever and swollen lymph nodes while evading the immune system through antigenic variation. If untreated, the disease advances to the neurological stage, where parasites invade the central nervous system, leading to severe symptoms such as sleep disturbances, confusion, and potential coma.
Fig.2 Role of neutrophils in Trypanosoma Cruzi infection. (de Andrade, M.F., et al., 2018)
Drug Targets of African Trypanosomiasis
- Ergosterol Pathway and CYP51 Inhibitors: The enzyme sterol 14-alpha demethylase (CYP51) is essential for the parasite's survival. Anti-fungal triazole derivatives, including ravuconazole and posaconazole, have been tested as CYP51 inhibitors, though they have shown limited long-term effectiveness in clinical trials.
- Proteasome Inhibitors: Inhibitors like GNF6702 and GSK3494245 target the proteasome, a crucial component for protein degradation in the parasite. GNF6702 has shown potential in treating kinetoplast diseases, including Chagas disease.
- Tc80 Proteinase and Peptides: The enzyme prolyl oligopeptidase (Tc80) is secreted by the parasite and plays a key role in cell invasion. Competitive inhibitors of Tc80, such as peptidyl nitrile and peptidyl ketobenzothiazole, have been explored.
- Cysteine Peptidase and K777: Cruzipain, a lysosomal cysteine peptidase, has been targeted by K777, a vinyl sulfone derivative. K777 has shown to significantly reduce parasite-induced cardiac damage in vivo
- Carbonic Anhydrase (TcCA) Inhibitors: TcCA plays a vital role in the parasite's survival by influencing ion exchange and promoting growth. Various inhibitors, including sulfonamides, thiols, and hydroxamates, have been identified, demonstrating trypanocidal activity in vitro.
Vaccine Development of African Trypanosomiasis
Vaccine efforts focus on prophylactic and therapeutic strategies to reduce parasite burden and prevent disease progression, considering the challenge posed by parasite persistence and the need for unconventional immune responses.
|
Vaccine Type |
Immunogen/Antigen |
Adjuvant |
Immune Response |
| Subunit Vaccine |
Cruzipain (Cz) |
CpG-ODN, GM-CSF, MALP-2 |
Induces strong Th1 response, IgG2a antibodies, CTL activity |
| DNA Vaccine |
Tc52, Tc24, Tc80 |
CpG-ODN, c-di-AMP |
Promotes Th1/Th17 immune response, polyfunctional T cells (CD4+ IFN-γ+ TNF-α+) |
| Multicomponent Vaccine |
Cz, Tc52, Tc24 |
None or combined adjuvants |
Enhances immune response breadth, antigen-specific IgG and IgA response |
| Genetic Vaccine |
ASP-2, TS, TSA-1 |
CpG-ODN, IL-15 |
Strong CD8+ T cell response, long-term memory T cell response |
| Therapeutic Vaccine |
TSA-1, Tc24, ASP-2 |
MPLA, E6020 |
Enhanced anti-inflammatory response, reduced myocardial fibrosis and inflammation |
Our Services
At our company, we are proud to offer a comprehensive suite of services to support our clients in the development of innovative African trypanosomiasis vaccines and therapies. Our team of seasoned scientists, immunologists, and pharmacologists leverages state-of-the-art technologies and deep domain expertise to accelerate the progress of your projects.
In African trypanosomiasis therapy development, our team focuses on discovering and characterizing new antimicrobial agents, such as small molecules, peptides, and biologics, that target virulence factors. We also offer services to support the evaluation, optimization, and advancement of your therapeutic pipeline.
If you are interested in our services, please don't hesitate to contact us.
References
- Pérez-Molina JA and Molina I. "Chagas disease." Lancet. (2018). 391(10115): p. 82-94.
- de Andrade, M.F., et al., "Involvement of neutrophils in Chagas disease pathology." Parasite Immunol, (2018). 40(12): p. e12593.
- da Costa, K.M., et al., "Trypanosoma cruzi trans-Sialidase as a Potential Vaccine Target Against Chagas Disease." Front Cell Infect Microbiol, (2021). 11: p. 768450.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
