To identify potential vaccine candidates for the prevention of infection with the filarial nematode Onchocerca volvulus, we screened an O. volvulus L3 stage cDNA library with sera from putatively immune (PI) subjects, and a prominent immunogenic clone of 1,184 nucleotides was identified. It contained an open reading frame of 363 amino acids encoding the glycolytic enzyme fructose 1,6 bisphosphate aldolase (Ov-fba-1). Immunolocalization experiments demonstrated that the protein was most abundantly expressed in metabolically active tissues, including body wall muscle and the reproductive tract of adult female worms. Immunoelectron microscopy of L3 demonstrated binding in the region where the cuticle separates during molting, in the channels connecting the esophagus to the cuticle, and in the basal lamina surrounding the esophagus and the body cavity. Among subjects from areas where this organism is endemic specific humoral and cellular immune responses to recombinant protein were observed in both PI and infected subjects, whereas responses were not observed among subjects who had not been exposed to O. volvulus. Despite the absence of differential responsiveness in parasite-exposed human populations, when the recombinant was tested for protective efficacy in a mouse chamber model, a reduction in survival of larvae by ca. 50% was seen. This observation provides support for the further study of this parasite enzyme as a vaccine candidate in larger animal models.Despite vector control and the widespread use of ivermectin in areas where Onchocerca volvulus is endemic, onchocerciasis continues to occur in significant parts of Africa and small pockets in Latin America. Recent epidemiologic studies indicate that, while chemotherapy with ivermectin results in relief of symptoms, community-based ivermectin distribution and vector control may not result in the eradication of infection (22).In order to identify novel larval-stage antigens as potential vaccine candidates, an O. volvulus L3 stage cDNA library was screened with pooled sera from a well-defined human population residing in region of Ecuador where onchocerciasis is endemic (8). Prominent among the multiple reactive recombinants identified by immunologic screening were isolates encoding fructose 1,6 bisphosphate aldolase (Ov-fba-1). We therefore undertook detailed characterization of this filarial enzyme and tested it for protective efficacy in an animal model of onchocerciasis. In so doing, we demonstrated its potential as a target for the induction of protective immunity to onchocerciasis. MATERIALS AND METHODSHuman sera. Sera were obtained from a group of O. volvulus-infected and putatively immune (PI) subjects from a region of Ecuador where the organism is endemic (8). Infection status was documented based on clinical history, nodule palpation, ophthalmologic evaluation for ocular microfilariae, and parasitologic evaluation through skin snip examination supplemented by PCR of the skin for an O. volvulus-specific repeat DNA sequence (28). Exposure to infection w...

To investigate whether helminth infections may affect the efficacy of vaccines by impairing the immune response to nonparasite vaccine antigens, we compared the antibody responses to tetanus toxoid (TT) after tetanus vaccination in 193 subjects with Onchocerca volvulus infection with 85 comparable noninfected controls. After vaccination, the proportions of subjects in each group attaining protective levels of antitetanus antibodies were similar (96.9% infected versus 97.6% noninfected). Postvaccination increases in antitetanus immunoglobulin G (IgG) and the predominant IgG isotype, IgG1, were equivalent in both groups, as were increases in specific IgG4 and IgE; however, significantly greater increases in specific IgG2 (P < 0.05) and IgG3 (P < 0.001) were observed in the noninfected group. Stratification of the O. volvulus-infected group into two groups representing light and heavy infections revealed a significantly impaired antitetanus IgG response in those with heavy infections compared to those with light infections (P < 0.01) or no infection (P < 0.05). The impact of concurrent intestinal helminth infections on the antitetanus response was also examined; an increased IgG4/IgE ratio was seen in those infected withStrongyloides stercoralis (P < 0.05) and when all helminth infections were combined as a single group (P < 0.05). These findings indicate that concurrent infection with O. volvulus does not prevent the development of a protective antitetanus response, although heavier O. volvulus infections are able to alter the magnitude of this response, and concurrent helminth infections (O. volvulusand intestinal helminths) may alter TT-specific antibody isotype responses.

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