The rolling out of a vaccine and more effective therapeutics for onchocerciasis is a critical step toward the goal of eradicating this terrible disease. As a research service provider, Protheragen offers comprehensive services in the development of vaccines and therapeutics for onchocerciasis.
Overview of Onchocerciasis
Onchocerciasis is referred to as ‘river blindness’ and is a dreadful neglected tropical disease caused by a filarial nematode, Onchocerca volvulus. Infection occurs from parasitic blackflies which has the potential to cause irreversible blindness and severe skin diseases. It poses a health hazard and creates socio-economic consequences for millions of people across the globe.
Global health experts estimate about 32 million Onchocerciasis cases exist with nearly 385,000 of these people blind even before the implementation of Mass Drug Administration (MDA) programmes. This disease is important in the public health context and is regionally concentrated in sub-Saharan Africa, where it constitutes a considerable threat, resulting in 1.23 million years of disability claimed by the effects of this untamed disease.
Fig.1 Phases in the elimination of human onchocerciasis. (Lakwo T., et al., 2020)
Vaccine Development for Onchocerciasis
Immunological and genomic techniques have enabled the identification of numerous antigens that could be candidates for vaccination. Some of them include:
- Ov-CPI-2 (Ov7): This antigen which is part of cystatin superfamily is recognized by sera from individuals believed to have immunity against the disease.
- Ov-RAL-2: This antigen is connected with protective immunity and is active in the immune response to O. volvulus.
- Ov-103: A surface-associated immunodominant antigen that has been shown to confer protective immunity in mice.
- Ov-ALT-1: A larval stage-specific antigen that has exhibited partial protection toward infection with O. volvulus.
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 use of ivermectin, a microfilaricidal drug used to treat the parasitic stage of onchocerciasis, has been the first line of defense relied on for treating onchocerciasis for a long time now. Prolonged dependency on these therapeutics and emerging drug resistance make alternative therapies mandatory:
Doxycycline
This antibiotic has macrofilaricidal effects through targeting the Wolbachia endosymbiotic bacteria, effectively sterilizing the adult worms.
Moxidectin
This broad-spectrum microfilaricidal drug is stronger than ivermectin; moxidectin suppresses the microfilarial form of the parasite to a greater extent than it.
- Emerging Therapies
To overcome the drawbacks of currently used therapeutics, new drugs are under development:
Flubendazole
Flubendazole is a drug that inhibits the polymerization of tubulin. It has great promise for killing adult filarial worms but is limited by oral bioavailability and high embryotoxicity.
Anti-Wolbachia Drugs
Flubentylosin and AWZ1066S are currently targeting the Wolbachia endosymbiont of O. volvulus and are undergoing clinical trials. This also targets the parasite itself as it is vital 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 full range research services cover all aspects of onchocerciasis drug and vaccine development, including antigen discovery and preclinical testing.
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.
