Enhanced protective Immunity Against Filariasis
Keywords: Tropical Medicine, Filariasis, Onchocerciasis, Onchocerca, volvulus, ochengi, Lymphatic, Wuchereria, Loa, Litomosoides, transcriptomes, microarrays, systems biology, bioinformatics, immunity, vaccination
Filarial infections remain a major public health problem in West and Central Africa. Three filarial species are involved: Onchocerca volvulus (onchocerciasis or river blindness); Wuchereria bancrofti (lymphatic filariasis); and Loa loa (the eye worm). These infections can be treated with a single dose of ivermectin and mass treatment with this drug has proved a successful strategy for controlling onchocercaisis as a public health problem in many regions. However, emergence of drug resistance and risk of severe adverse reactions associated with L loa co-infections is restricting the implementation of mass treatment and consequently alternate approaches to control are required and an obvious approach would be vaccination.
The feasibility of vaccination against filarial infections is founded on two pillars. First, identification of individuals who have lived for many years with constant exposure to infection yet never present with either clinical or parasitological signs of infection, Second, successful immunisation of animal models against experimental and natural challenge through vaccination with irradiated infective L3 larvae.
Studies with animal models have identified antibody-dependent cell-mediated processes (Th2) as basis of protective immunity. These same processes have been identified in immune humans. Furthermore, human studies have also drawn attention to immune regulatory processes that influence clinical outcome of infection. These observations provide a basis for vaccine development.
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To identify the antigens (vaccine candidates) that stimulate protective immunity and ensure their appropriate formulation and delivery to promote protective responses and avoid any pathology.
Cohorts of onchocerciasis patients who have received treatment with ivermectin or tetracycline, or are co infected with either W bancrofti or L loa provide both input to the pathway studies and a means of validation of the computer assimilations. Confirmation of the mechanisms and targets of protective immunity and validation of computer assimilations will also be investigated using the O ochengi-cattle model that also enables experimentation under natural challenge. Litomosoides sigmodontis in mice provides a robust and rapid validation of results obtained from computation relating to expression and regulation of protective responses and a primary system for screening vaccine candidates