A vaccine candidate for onchocerciasis

April 25th 2019

Researchers at the Biopark have developed a vaccine candidate for onchocerciasis and other filariases. This multi-epitope chimeric protein was designed using bioinformatic tools.

Onchocerciasis, also known as ‘river blindness’, is a parasitic disease transmitted by the Simulium blackfly. The parasite species infect humans and cattle and inflicts a huge socio-economic burden in a number of sub-Saharan African countries. This is because the symptoms of onchocerciasis in humans include (potentially permanent) blindness and skin lesions, which results in patients being stigmatised.

A ‘sedated’ immune system
In its initial larval form (microfilaria), the parasite can be killed using specific drugs. However, there is still no treatment for adult worms, which can live 15 to 18 years! ‘The parasite secretes molecules that numb the host’s immune system’, explains Professor Jacob Souopgui, head of ULB’s Laboratory of Embryology and Biotechnology at the Biopark. ‘But in areas where onchocerciasis is endemic, around 5% of the population develop an immunity after being in contact with the parasite, which proves the immune system has the ability to fight it.’ The question, though, is how and using what mechanisms.?

Screening with bioinformatics
Professor Souopgui and his team first studied a receptor in the parasite as a potential therapeutic and diagnostic target. In the context of diagnosis, epitopes (1) were predicted using bioinformatics tool, validated experimentally and published in PLOS ONE journal. The results obtained from this work motivated the use of the same approach towards vaccine design. Therein lies the originality of their approach: ‘Within a single antigen, certain epitopes stimulate the immune system while others weaken it’, explains Professor Souopgui. ‘This explains why certain “intact” antigens fail to immunise the subject. We can avoid this by selecting only epitopes that trigger a protective immune response.’

A chimeric epitope-based vaccine candidate
The research team was able to predict humoral and cellular response inducing-epitopes (2) in order to create a chimeric multi-epitope vaccine candidate. ‘Both humoral and cellular responses to this this protein could potentially help in the fight against onchocerciasis, but also other types of filariasis (3), such as loiasis.’? The discovery was published in Scientific Reports.
The next steps will be to test the candidate vaccine on serum from immune subjects and put it in contact with parasites found in bovines. ‘By collaborating with our colleagues in Cameroon, we may be able to vaccinate livestock in their country’, hopes Professor Souopgui. ‘If this initial experiment is successful, we may move on to clinical trials.’

(1) An antigen is made up of several epitopes, which are polypeptides that can trigger an immune response or prevent it.
(2) The immune system has a cellular component that can innately recognise ‘non-self’, and a humoral component that produces specific antibodies.
(3) Filariases are diseases caused by filarial parasites.