Antibody- and complement-mediated immunity to infective and autoinfective third stage larvae of Strongyloides stercoralis

Strongyloides stercoralis is a parasitic nematode that infects tens of millions of people throughout the world causing disease ranging from relatively asymptomatic to fatal disseminated hyperinfection. It was determined that mice immunized against S. stercoralis third stage larvae (L3) could kill greater than 90% of challenge L3 contained within diffusion chambers. The goals of the present study were to identify the host components responsible for protective immunity, determine the stage specificity of the response and determine if unique antigens are targeted by the protective response. Serum from immune mice was able to transfer complete immunity against challenge infection. The transferred immunity could be ablated by excluding cells from the larval microenvironment or by depleting granulocytes or eosinophils in recipient mice. Transfer of fractionated serum found that only IgM confers immunity, which was also the only isotype found to bind to the surface of L3 in vivo. Activated C3 also bound to the surface of L3 in vivo. This C3 binding was blocked by complement depletion through cobra venom factor treatment, which also ablated immunity. This immunity to L3 did not kill autoinfective L3 (L3a) in challenge infections but could kill the host adapted L3 (L3$\sp+).$ While immunity was specific to the L3-L3$\sp+$ stages, many common as well as unique antigens of L3, L3$\sp+$ and L3a were recognized by immune serum. Thus, immune IgM and complement in conjunction with eosinophils protect mice from larval infection. Additionally, the antigens recognized by IgM in immune serum may indicate potential vaccine candidates