Protective immunity linked with a distinct developmental stage of a filarial parasite

Repeated low dose infections of the jird Meriones unguiculatus, with the filarial parasite Acanthocheilonema viteae cause a substantial reduction of the total worm burden, suggesting a parasite-driven immune mechanism that controls super-infections. Quantitative recovery of parasites from tissues of triple infected jirds reveals that the larvae derived from a subsequent challenge infection are inactivated or severely impaired several days after transmission, precisely during their molt from the L3 to the L4 stage. Moreover, only larvae undergoing the molt from L3 to L4 stages are capable of stimulating an immune response directed against the challenge infection, indicating that protective Ag are produced during the molting period. Consistent with this, inactivated L3 or live L4 do not produce the same effect. In contrast to susceptible animals, immune jirds elicit high serum antibody titers against molting Ag. Indirect fluorescence antibody-binding tests with sera from protected jirds reveal specific labeling of the surface of molting L3 and not other larval stages, implying a stage-specific elimination process. The identification of molting L3 as a natural target for host immune mechanisms, emphasizes the central importance of this larval stage for future efforts aimed toward the development of a filarial vaccine.