Onchocerciasis Vaccine TOVA Initiative

PAI Life Sciences is collaborating with The Onchocerciasis Vaccine for Africa (TOVA) Initiative

With our collaborators at The Onchocerciasis Vaccine for Africa (TOVA) Initiative we  are working on two major lead candidates for protective vaccination: Ov-103, and Ov-RAL-2 that are protective in model disease and have minimal risk of inducing detrimental IgE responses in children. Our research is moving these candidates forward to human testing with support from the National Institutes of Health.

Children leading their parents who have been blinded by onchocerciasis.

Onchocerciasis: Endangering 120 Million People Every Year

Colour-enhanced Scanning Electron Micrograph (SEM) of Onchocerca volvulus, image of a female worm with microfilaria. O. volvulus is a nematode that causes onchocerciasis, or river blindness, mostly in Africa. Long-term corneal inflammation, or keratitis, leads to thickening of the corneal stroma which ultimately leads to blindness.

Onchocerciasis or river blindness is a human disease caused by the filarial worm Onchocerca volvulus, and it endangers approximately 120 million people each year globally. When the worms become adults, they can live for over a decade in knots (“nodules”) under the skin and release millions of of smaller worms or microfilariae. Circulating microfilariae cause many clinical symptoms including persistent, debilitating itching, severe dermatitis or skin inflammation, and lesions in the eye that can result in the blindness which is a trademark that has become part of the worms’ name. The way the illness manifests is controlled by the immune response of the body to the parasite, a fact we are trying to leverage when designing a vaccine for this disease.

New estimates indicate that 17 million cases of onchocerciasis occur worldwide each year and up to 1.2 million of these cases result in vision impairment and blindness. Today, more than 99% of the world’s onchocerciasis cases occur in sub-Saharan Africa.

Onchocerciasis is a scourge that continues to impose a global health burden of and adjusted 1.18 million years lived with disability, and it has long been the focus of efforts to alleviate results of the illness and the resulting lost productivity. 

Why Does This Disease Need New Research Approaches?

The lead drug to treat the disease, ivermectin, has been hugely successful, but it is only effective against the worms that cause blindness and dermatitis, but has little activity against the long-lived adult worms. Drugs that eliminate adult worms by targeting the symbiotic bacteria have been developed, but they have limited populations in which they can be used.

Concomitant immunity in infected humans is acquired with age and prevents most of the newly acquired infections from developing resulting in a stable adult worm burden. There is reason for concern that with continued ivermectin treatment concomitant immunity will disappear. Studies in humans and cattle have shown that infected hosts in which infections were cleared by chemotherapy, acquired new infections of equal or higher intensity than before the therapeutic intervention. Therefore, it is possible in the long run that control programs using the drug could in the long run exacerbate the disease if complete elimination is not achieved.

Another deficiency of drug treatment programs is the fact that ivermectin cannot be used in areas co-endemic with loiasis (L. loa infection) due to the risk of severe adverse events, especially toxic encephalopathy. This situation both blocks elimination efforts in Loa-affected communities – particularly in 11 Central African countries – where 12 million people live in co-endemic zones, and also creates reservoir onchocerciasis infections that potentially could promote the reintroduction of onchocerciasis in neighboring communities under control programs.

A major concern is the potential widespread emergence of partially or completely drug-resistant O. volvulusand Dirofilaria immitis, which poses a threat to the long-term effectiveness of using ivermectin alone in all areas.