Onchocerca volvulus: The Road from Basic Biology to a Vaccine

Abstract

Human onchocerciasis - commonly known as river blindness - is one of the most devastating yet neglected tropical diseases, leaving many millions in sub-Saharan Africa blind and/or with chronic disabilities. Attempts to eliminate onchocerciasis, primarily through the mass drug administration of ivermectin, remains challenging and has been heightened by the recent news that drug-resistant parasites are developing in some populations after years of drug treatment. Needed, and needed now, in the fight to eliminate onchocerciasis are new tools, such as preventive and therapeutic vaccines. This review summarizes the progress made to advance the onchocerciasis vaccine from the research laboratory into the clinic.

Keywords: Onchocerca volvulus; elimination; vaccine; vaccine candidates.

Figure 1

The Onchocerca volvulus lifecyle. During a blood meal, an infected blackfly (genus Simulium) introduces third-stage filarial larvae onto the skin of the human host, where they penetrate into the bite wound ➊. In subcutaneous tissues the larvae ➋ develop into adult filariae, which commonly reside in nodules in subcutaneous connective tissues ➌. Adults can live in the nodules for approximately 15 years. Some nodules may contain numerous male and female worms. Females measure 33 to 50 cm in length and 270 to 400 μm in diameter, while males measure 19 to 42 mm by 130 to 210 μm. In the subcutaneous nodules, the female worms are capable of producing microfilariae for approximately 9 years. The microfilariae, measuring 220 to 360 μm by 5 to 9 μm and unsheathed, have a life span that may reach 2 years. They are occasionally found in peripheral blood, urine, and sputum but are typically found in the skin and in the lymphatics of connective tissues ➍. A blackfly ingests the microfilariae during a blood meal ➎. After ingestion, the microfilariae migrate from the blackfly’s midgut through the hemocoel to the thoracic muscles ➏. There the microfilariae develop into first-stage larvae ➐ and subsequently into third-stage infective larvae ➑. The third-stage infective larvae migrate to the blackfly’s proboscis ➒ and can infect another human when the fly takes a blood meal ➊. Reproduced from the Center for Disease (https://www.cdc.gov/dpdx/onchocerciasis/index.html).

Figure 2

Schematics that illustrates the down-selection process that resulted in the selection of the two most promising vaccine antigens for future clinical development.

Figure 3

Combining a systems analysis of response to vaccines and machine learning algorithms to help predict vaccine efficacy. (A) Applying machine learning to experimental infections across multiple model systems and species can help identify which immune variables throughout the time course of an infection most reliably predict infection load, while ensuring the trained models generalize well across biological systems. (B) These optimized models may then be useful in predicting vaccine efficacy in human trials in two ways: identifying what data to collect and predicting likely vaccine efficacy using incomplete data that are typical of human field studies.