TROPOMYOSIN IMPLICATED IN HOST PROTECTIVE RESPONSES TO MICROFILARIAE IN ONCHOCERCIASIS

A cDNA from adult female Onchocerca volvulus encoding the C-terminal p ortion of a tropomyosin isoform (termed MOv-14) has been shown previou sly to confer protective immunity in rodent models of onchocerciasis. The full-length sequence (designated Ov-tmy-1) obtained by PCR amplifi cation, codes for a protein of 33 kDa and shares 91% identity with tro pomyosins from other nematodes, falling to 57% identity with human alp ha-tropomyosin. Ov-TMY-1 migrates with an apparent molecular mass of 4 2 kDa on SDS/PAGE and is present in all life-cycle stages, as determin ed by immunoblotting. Immunogold electron microscopy identified antige nic sites within muscle blocks and the cuticle of microfilariae and in fective larvae. Anti-MOv14 antibodies were abundant in mice exhibiting serum-transferable protection against microfilariae conferred by vacc ination with a PBS-soluble parasite extract. In contrast, little or no MOv14-specific antibody was present in mice inoculated with lire micr ofilariae, in which resistance is mediated by antibody-independent mec hanisms. In human infections, there was an inverse correlation between anti-tropomyosin IgG levels and densities of microfilariae in the ski n. Seropositivity varied with the relative endemicity of infection, An immunodominant B cell epitope within OV-TMY-1 (AQLLAEEADRKYD) was map ped to the N terminus of the MOv14 protein by using sera from protecti vely 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 dete cted in human infections. It is concluded that antibody responses to t ropomyosin may be important in limiting microfilarial densities in a p roportion 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.