A cDNA from adult female Onchocerca volvulus encoding the C-terminal portion of a tropomyosin isoform (termed MOv-14) has been shown previously to confer protective immunity in rodent models of onchocerciasis. The full-length sequence (designated Ov-tmy-1) obtained by PCR amplification, codes for a protein of 33 kDa and shares 91% identity with tropomyosins from other nematodes, falling to 57% identity with human ␣-tropomyosin. Ov-TMY-1 migrates with an apparent molecular mass of 42 kDa on SDS͞PAGE and is present in all life-cycle stages, as determined by immunoblotting. Immunogold electron microscopy identified antigenic sites within muscle blocks and the cuticle of microfilariae and infective larvae. Anti-MOv14 antibodies were abundant in mice exhibiting serum-transferable protection against microfilariae conferred by vaccination with a PBSsoluble parasite extract. In contrast, little or no MOv14-specific antibody was present in mice inoculated with live microfilariae, in which resistance is mediated by antibodyindependent mechanisms. In human infections, there was an inverse correlation between anti-tropomyosin IgG levels and densities of microfilariae in the skin. Seropositivity varied with the relative endemicity of infection. An immunodominant B cell epitope within Ov-TMY-1 (AQLLAEEADRKYD) was mapped to the N terminus of the MOv14 protein by using sera from protectively vaccinated mice. Intriguingly, the sequence coincides with an IgE-binding epitope within shrimp tropomyosin, believed to be responsible for hypersensitivity in individuals exhibiting allergy to shellfish. IgG and IgE antibodies reacting with the O. volvulus epitope were detected in human infections. It is concluded that antibody responses to tropomyosin may be important in limiting microfilarial densities in a proportion of individuals with onchocerciasis and have the potential to mediate hypersensitivity reactions to dead microfilariae, raising the possibility of a link with the immunopathology of infection.

A cDNA designated MOv2 was isolated from an Onchocerca volvulus library on the basis of its product's recognition by an antiserum raised against the infective stage. Immunogold electron microscopy revealed a high density of antigenic sites associated with the annulae of the L3 cuticle and with the uterine wall of the adult female: a general, low density of labelling occurred in all developmental forms. Western blotting confirmed the presence of the antigen throughout the life cycle and the existence of an immunologically cross-reactive homologue in the related filaria, Acanthocheilonema viteae. The antigen was shown to be secreted by infective larvae and adult females of A. viteae. Sequence comparisons revealed two homologues of MOv2 (Ov-20, Ov-9) which had been selected independently by other laboratories on the basis of their specific recognition by human onchocerciasis infection sera. The IgG antibody response against MOv2 in cattle experimentally infected with O. lienalis revealed the induction of a response during the prepatent period that was strongly boosted at the onset of patency. However, only a proportion of infected cattle responded with a detectable level of anti-MOv2 antibodies. The appearance of MOv2 in larval cuticle and secretions prompted us to evaluate it as a candidate molecule for prophylactic immunization. Trials performed in the A. viteae/Mongolian jird model of filariasis revealed that recombinant MOv2 induced a host-protective response, reducing worm recoveries by 36-55% following a challenge infection.