The abundant larval transcript-1 and-2 genes of Brugia malayi encode stage-specific candidate vaccine antigens for filariasis

Lymphatic filariasis is a major tropical disease caused by the mosquito-bor ne nematodes Brugia and Wuchereria, About 120 million people are infected a nd at risk of lymphatic pathology such as acute lymphangitis and elephantia sis. Vaccines against filariasis must generate immunity to the infective mo squito-derived third-stage larva (L3) without accentuating immunopathogenic responses to lymphatic dwelling adult parasites. We have identified two hi ghly expressed genes, designated abundant larval transcript-1 and -2 (alt-1 and alt-2), from each of which mRNAs account for >1% of L3 cDNAs, ALT-1 an d ALT-2 share 79% amino acid identity across 125 residues, including a puta tive signal sequence and a prominent acidic tract. Expression of alt-1 and alt-2 is initiated midway through development in the mosquito, peaking in t he infective larva and declining sharply following entry into the host. Hum ans exposed to Brugia malayi show a high frequency of immunoglobulin G1 (Ig G1) and IgG3 antibodies to ALT-1 and -2, distinguishing them from adult-sta ge antigens, which are targeted by the IgG4 isotype, Immunization of suscep tible rodents (jirds) with ALT-1 elicited a 76% reduction in parasite survi val, the highest reported for a single antigen from any filarial parasite, ALT-1 and the closely related ALT-2 are therefore strong candidates for a f uture vaccine against human filariasis.