Abstract
The intestinal nematode Baylisascaris schroederi is an important cause of death for wild and captive giant pandas. Inorganic pyrophosphatases (PPases) are critical for development and molting in nematode parasites and represent potential targets for vaccination. Here, a new PPase homologue, Bsc-PYP-1, from B. schroederi was identified and characterized, and its potential as a vaccine candidate was evaluated in a mouse challenge model. Sequence alignment of PPases from nematode parasites and other organisms show that Bsc-PYP-1 is a nematode-specific member of the family I soluble PPases. Immunohistochemistry revealed strong localization of native Bsc-PYP-1 to the body wall, gut epithelium, ovary and uterus of adult female worms. Additionally, Bsc-PYP-1 homologues were found in roundworms infecting humans (Ascaris lumbricoides), swine (Ascaris suum) and dogs (Toxocara canis). In two vaccine trials, recombinant Bsc-PYP-1 (rBsc-PYP-1) formulated with Freund complete adjuvant induced significantly high antigen-specific immunoglobulin (Ig)G but no IgE or IgM responses. Analysis of IgG-subclass profiles revealed a greater increase of IgG1 than IgG2a. Splenocytes from rBsc-PYP-1/FCA-immunized mice secreted low levels of T helper (Th)1-type cytokines, interferon-γ and interleukin (IL)-2, while producing significantly high levels of IL-10 and significantly elevated levels of IL-4 (Th2 cytokines) after stimulation with rBsc-PYP-1 in vitro. Finally, vaccinated mice had 69.02–71.15% reductions (in 2 experiments) in larval recovery 7 days post-challenge (dpc) and 80% survival at 80 dpc. These results suggest that Th2-mediated immunity elicited by rBsc-PYP-1 provides protection against B. schroederi, and the findings should contribute to further development of Bsc-PYP-1 as a candidate vaccine against baylisascariasis.
Highlights
Baylisascariasis is a neglected zoonotic helminthic disease caused by parasitic nematodes of the genus Baylisascaris (Nematoda: Ascaridida) with great medical and veterinary significance worldwide [1,2,3]
Islam et al showed in an A. suum mouse infection model that vaccination with the E. coli-expressed recombinant antigen rAsPPase could confer significant hostprotective immunity against parasite challenge [23]
Extensive protein database searches revealed that the deduced amino acid sequence of Bsc-PYP-1 is highly similar to the A. suum PPase protein AdR44 and moderately similar to PPase homologues from other nematode species, while failing to share comparable levels of similarity with any available PPase proteins from mammals, including the giant panda, the specific host of B. schroederi (Figure 1A)
Summary
Baylisascariasis is a neglected zoonotic helminthic disease caused by parasitic nematodes of the genus Baylisascaris (Nematoda: Ascaridida) with great medical and veterinary significance worldwide [1,2,3]. The causative pathogens, Baylisascaris spp., are widely distributed in the giant panda (Ailuropoda melanoleuca), red panda (Ailurus fulgens), raccoon (Procyon lotor), Ursid species (Ursus maritimus, Ursus arctos pruinosus, Selenartos thibetanus mupinensis and Ursus arctos lasiotus) and other mammals including humans and can lead to severe clinical visceral (VLM), ocular (OLM) and neural without intermediate hosts. This parasite (at the adult stage) usually inhabits the intestines of the giant panda, while its migrating larvae may disseminate into various body tissues. Target antigens that play crucial roles in the survival, development and reproduction of parasitic nematodes would be an ideal control strategy
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