The Onchocerciasis Vaccine for Africa (TOVA): A new tool to help prevent, control and eliminate river blindness from Africa.
The International Community has set ambitious targets for elimination of onchocerciasis (river blindness) as a public health problem by 2025. Considerable progress has been made through annual and bi-annual mass treatment with ivermectin (MectizanTM) for periods of between 10 and 15 years. However, in areas of high prevalence, transmission of the infection persists after 20 years of mass treatment. Furthermore, disease modelling studies suggest that it may not be possible to achieve complete onchocerciasis elimination using ivermectin alone, even after 50 years of annual treatment (https://doi.org/10.1371/journal.pntd.0003664; https://doi.org/10.1371/journal.pntd.0002169).
WHO defines elimination as the reduction to zero of the incidence of an infection caused by a specific pathogen in a defined geographical area, with minimal risk of reintroduction. This is not eradication, which is the permanent [complete] removal a disease from the World.
If elimination of onchocerciasis is to be achieved on a more extensive scale, new and additional interventions will be required. A vaccine would complement and augment ivermectin treatment and address identifiable deficiencies in current ivermectin-based control programmes which exclude children under 5 years and cannot used in communities where onchocerciasis is co-endemic with loiasis, a second parasitic infection.
TOVA partners have been working towards the development of a vaccine for over 25 years. Three vaccine candidates have been selected based on their ability to evoke strong protective responses capable of reducing parasite burden of immunised animals by more than 90%.
TOVA aims to take at least one of these vaccine candidate through Phase I trials by 2025. The immediate task is to manufacture the vaccines and demonstrate their safety in accordance with national and international regulations and WHO guidelines.
The onchocerciasis vaccine is initially aimed at protecting pre-school children (<5 years of age). The vaccine will reduce adult worm burden and fecundity with consequential reduction in pathology associated with microfilariae.
In addition, a vaccine will find use in ongoing ivermectin control programmes and contribute to reduction in transmission rates; moreover, it will protect areas where local elimination may have been achieved.
Onchocerciasis is a parasitic disease caused by the filarial worm Onchocerca volvulus. The infection is transmitted through the bite of blackflies (Simulium spp) that breed in fast flowing streams and rivers, and it is this association that gave rise to the common name of the disease.
According to the World Health Organisation (WHO, 2017), 21 million people are infected with O volvulus worldwide and 198 million are at risk of infection. More than 99% of onchocerciasis patients live in West and Central Africa, although there are also small isolated foci in Latin America and Yemen.
Infection is initiated by L3 larvae that enter the skin when blackflies take a blood meal . Over a period of about 1 year, L3 larvae mature into adults which are found in sub-cutaneous nodules over the pelvis, pectoral girdle and/or head. Female worms live for about 15 years and can give birth to between 500 and 1500 microfilariae larvae per day. Microfilariae migrate from the nodules to the skin and eyes where they can be detected within a year of the initial infection. The parasite’s life cycle is completed when microfilariae are ingested by blackfly taking a blood meal.
Microfilariae can live up to two years in the skin but when they eventually die they evoke inflammatory responses, which are responsible for most symptoms of onchocerciasis. Itching is the most frequent early sign of infection but this can lead to severe local or general and disfiguring dermatitis and premature ageing of the skin. Skin disease has a disproportionate impact on women, first through social exclusion, including reducing prospects of marriage; and second, on their ability and willingness to breast feed babies.
About 1% of individuals infected with O volvulus are blind and a further 10% visually impaired, however, up to 70% suffer from skin disease of varying severity.
Current control (and treatment) of onchocerciasis relies on use ivermectin (mectizanTM) in community-directed mass treatment programs, such as those previously run through the African Programme for Onchocerciasis Control, APOC).
Adult parasites live for up to 15 years in subcutaneous nodules from where they release, into the skin, many thousands of microscopic larvae known as microfilariae. Inflammatory responses associated with microfilariae are the cause of the disease. Microfilariae are also the life cycle stage that are ingested by the blackfly and thereby ensure continued transmission of the infection.
The Onchocerciasis Vaccine for Africa (TOVA)
This Initiative was launched as a response to the London Declaration on Neglected Tropical Diseases; and, the scientific and technical demands for new tools to complement and augment use of ivermectin to ensure elimination of onchocerciasis from Africa.
TOVA has its origins in the river blindness (onchocerciasis) vaccine program of the Edna McConnell Clark Foundation (1985-1999) and subsequently supported by European Union through its Directorate-General for Research and the US NIH National Institute of Allergy and Infectious Diseases. These investments have combined development of animal models and human studies of protective immunity with molecular and post genomic analyses of filarial parasites.
Three vaccine candidates have been identified through their proven efficacy in three different filarial animal models in five independent laboratories. TOVA aims to take at least one of these experimental vaccines through phase 1 safety trials by 2024.
It is envisaged that the onchocerciasis vaccine will be used initially to protect children (<5 years of age) living in loiasis co-endemic areas where current treatment with ivermectin is contra-indicated because of the risk of severe adverse reactions. The vaccine will reduce adult worm burden and fecundity with consequential reduction in pathology associated with microfilariae. In addition, a vaccine will find use in ongoing ivermectin treatment programs and contribute to reduction in transmission rates.