Characterization of a secreted antigen of Onchocerca volvulus with host‐protective potential

Abstract

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.

Expression and Secretion of a Larval-specific Chitinase (Family 18 Glycosyl Hydrolase) by the Infective Stages of the Parasitic Nematode, Onchocerca volvulus

“…Immunogold Electron Microscopy with O. volvulus-Adult worms within nodules, developing larvae within blackflies (from day 1 to day 8 post-transmission), and post-infective larvae in culture (described below) were fixed in 2% paraformaldehyde, 0.5% glutaraldehyde in 0.075 M sodium cacodylate buffer and embedded for immunoelectron microscopy, as described (26). Sections (90 nm) mounted on Formvar-coated nickel grids were reacted with rabbit antisera to recombinant Ov-CHI-1 serially diluted from 1:200 to 1:1000 in 1% bovine serum albumin, 0.01% Tween 20 in phosphate-buffered saline.…”

A Comprehensive, Model-Based Review of Vaccine and Repeat Infection Trials for Filariasis

“…Several Onchocerca antigens have been evaluated in this model, including two that can be detected in A. viteae ES products (OvB20, and MOv2) and one that is a subunit of O. volvulus tropomyosin (MOv14) (28)(29)(30). All of these antigens induced moderate protection (36 to 60%) against adult worm burdens and exceptional protection against microfilaremia (89 to 97%).…”

Development of a Recombinant Antigen Vaccine against Infection with the Filarial WormOnchocerca volvulus

“…Studies with other filarial worms have shown that recombinant antigens can be identified with antibodies from immune serum and that these antigens induced a protective immune response against larval parasites, killing approximately 50% of parasites in the challenge infections (26,35,49). The advantage of using defined recombinant antigens lies in the fact that they can be efficiently and reproducibly generated, whereas irradiated larvae or crude native antigen preparations cannot be practically generated and therefore lack clinical utility.…”