Haemonchus contortus GA1 antigens: Related, phospholipase C-sensitive, apical gut membrane proteins encoded as a polyprotein and released from the nematode during infection

It was previously shown that the Haemonchus contortus apical gut surface proteins p46, p52, and p100 induced protective immunity to challenge infections in goats. sere, it is shown that the three proteins are all encoded by a single gene (GA1) sand initially expressed in adult parasites as a polyprotein (p100(GA1)), p46(GA1) and p52(GA1) are related proteins with 47% sequence identity, including a cysteine-containing region, which appears to confer secondary structure to these proteins, and a region with sequence similarity to bacterial Tolb proteins. GA1 protein expression is regulated during the life cycle at the level of transcript abundance. Only p52(GA1) has characteristics of a glycosylinositolphospholipid membrane-anchored protein. However, both p46(GA1) and p52(GA1) were released from tire gut membrane by phosphatidylinositol specific-phospholipase C, suggesting that p46(GA1) membrane association depends on interactions with a glycosylinositolphospholipid gut membrane protein. Finally, GA1 proteins occur in abomasal mucus of infected lambs, demonstrating possible presentation to the host immune system during H. contortus infection. The results identify multiple characteristics of the GA1 proteins that should be considered for design of recombinant antigens for vaccine trials and that implicate a series of cellular processes leading to modification and expression of GA1 proteins at the nematode apical gut surface.