The development of a vaccine and improved therapeutics for onchocerciasis is crucial for the global effort to eliminate this debilitating disease. As a research service provider, Protheragen offers comprehensive services in the development of vaccines and therapeutics for onchocerciasis.
Overview of Onchocerciasis
Onchocerciasis, commonly known as river blindness, is a devastating neglected tropical disease caused by the filarial nematode Onchocerca volvulus. This parasitic infection, transmitted through the bite of infected blackflies, can lead to irreversible visual impairment, blindness, and debilitating skin conditions, adversely impacting the lives of millions worldwide.
Onchocerciasis is a significant global health concern, with an estimated 32 million people infected and 385,000 suffering from blindness prior to the implementation of mass drug administration (MDA) programs. The disease is primarily prevalent in sub-Saharan Africa, where it remains a significant burden, contributing to an estimated 1.23 million years lost from disability due to its debilitating effects.
Fig.1 Phases in the elimination of human onchocerciasis. (Lakwo T., et al., 2020)
Vaccine Development for Onchocerciasis
Several antigens have been identified as potential vaccine candidates through immunological and genomic approaches:
- Ov-CPI-2 (Ov7): This antigen, belonging to the cystatin superfamily, is recognized by sera from individuals with putative immunity.
- Ov-RAL-2: This antigen is associated with protective immunity and is involved in the immune response against O. volvulus.
- Ov-103: An immunodominant surface-associated antigen that has been shown to induce protective immunity in mice.
- Ov-ALT-1: A larval stage-specific antigen that has demonstrated partial protection against O. volvulus infection.
Table 1. The characteristics of major vaccine candidates for onchocerciasis. (Zhan B., et al., 2022)
| Antigen |
Function(s) |
Localization |
Size |
Immune sera used to clone |
Protective evidence |
Expressed host |
Adjuvant |
Worm reduction % |
Immu effector |
| OvRAL-2 |
Novel, nematodespecific SXP/RAL-2 family |
Larval/adult hypodermis; ES |
17 kDa |
Rabbit antiL3, PI sera |
-Recognized by PI sera
-Ocular pathology |
E. coli |
BC/FCA
Alum |
51%–60%
39% (Hess) |
IgG1, IgG3 |
| Ov-103 |
Novel, surfaceassociate antigen |
Cuticle and hypodermis of L3, Mf |
15 kDa |
Chimpanzee infected sera |
Recognized by PI sera |
E. coli |
Alum |
8% |
|
| OvALT-1 |
Abundant larval transcript, secreted larval acidic protein |
L3 granules esophagus |
22 kDa |
PI sera |
-Recognized by PI
-Secreted
-L3-specific
-Protective homologue in B. mala |
E. coli |
Freund's
Alum |
36%
42%
combined with other 7 antigens |
IgG1, IgG3 |
| OvTMY-1 |
Tropomyosin |
Cuticle and muscle of microfilariae and L3 secreted |
33 kDa |
Recognized by protective immune sera |
-Antibody inversely correlated with the densities of Mf
-Protective homologue in O. lienalis and A. viteae |
E. coli fused with MBP |
Freund's |
48%–62% |
IgG |
Therapeutics Development for Onchocerciasis
- Current Therapies
The mainstay of onchocerciasis therapeutics has been ivermectin, a microfilaricidal drug that targets the microfilariae stage of the parasite. However, the need for repeated therapeutics and the emergence of drug resistance have prompted the search for alternative therapies:
Doxycycline
By targeting the endosymbiotic bacteria Wolbachia, doxycycline has shown macrofilaricidal activity, effectively sterilizing adult worms.
Moxidectin
A potent microfilaricidal drug that has demonstrated superior suppression of microfilarial levels compared to ivermectin.
- Emerging Therapies
New drugs are in development to address the limitations of current therapeutics:
Flubendazole
As an inhibitor of tubulin polymerization, flubendazole has shown potential in killing adult filarial worms but faces challenges due to its oral bioavailability and embryotoxicity.
Anti-Wolbachia Drugs
Flubentylosin and AWZ1066S are in clinical trials, targeting the Wolbachia endosymbiont of O. volvulus, which is essential for the parasite's survival and reproduction.
Our Services
At Protheragen, we are committed to accelerating the development of innovative solutions to combat onchocerciasis. Our comprehensive research services span the entire spectrum of onchocerciasis drug and vaccine development, from antigen discovery to preclinical evaluation.
Preclinical Research
- Pharmacodynamics Study Services
- Pharmacokinetics Study Services
- Drug Safety Evaluation Services
Disease Models
- BALB/c Mouse Model for Onchocerca ochengi Microfilariae (mf): Mice were infected with O. ochengi mf obtained from cattle skin.
- Mongolian Gerbil Model for Onchocerca ochengi Microfilariae (mf): Gerbils were infected with O. ochengi mf subcutaneously.
Our state-of-the-art facilities and experienced team of scientists leverage cutting-edge technologies and a deep understanding of the disease to provide our clients with tailored solutions. If you are interested in our services, please feel free to contact us.
References
- Lakwo Thomson, et al. "Onchocerciasis elimination: progress and challenges." Research and Reports in Tropical Medicine (2020): 81-95.
- Zhan, Bin, et al. "Advancing a human onchocerciasis vaccine from antigen discovery to efficacy studies against natural infection of cattle with Onchocerca ochengi." Frontiers in Cellular and Infection Microbiology 12 (2022): 869039.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
