Selective Drug Targets in Parasites

Kohler, Peter O.; Marhöfer, Richard J.

doi:10.1002/9783527626816.ch6

Cited by 3 publications

(1 citation statement)

References 57 publications

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“…For parasites, such as Ascaris roundworms, PPases are believed to be further involved in molting, as indicated in Ascaris suum by RNA-mediated interference and enzyme activity inhibition assays [ 23 , 24 ]. Considering the important roles of PPases in life processes of various organisms including parasitic nematodes, some of these enzymes have been selectively targeted for pharmaceutical and vaccine purposes [ 25 ]. For example, an adjuvanted recombinant PPase antigen from ascarids was recently demonstrated to induce a high level of protection (>70%) against A. suum challenge in mice, and its potential for use as a candidate vaccine against ascariasis is further suggested in pigs [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Potential of recombinant inorganic pyrophosphatase antigen as a new vaccine candidate against Baylisascaris schroederi in mice

Xie

Chen

Yan

et al. 2013

Vet Res

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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.

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Section: Introductionmentioning

confidence: 99%

Potential of recombinant inorganic pyrophosphatase antigen as a new vaccine candidate against Baylisascaris schroederi in mice

Xie

Chen

Yan

et al. 2013

Vet Res

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Drug Discovery Approaches toward Anti‐Parasitic Agents

Rohwer¹,

Marhöfer²,

Caffrey

et al. 2011

Apicomplexan Parasites

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Discovery and Development of Veterinary Antiparasitic Drugs: Past, Present and Future

Woods¹,

Vaillancourt

Wendt

et al. 2011

Future Med. Chem.

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Despite investment in programs to manage the development of resistance to existing agents, this continues to drive the need for discovery of novel antiparasitic agents for veterinary medicine. Historically, antiparasitic drug discovery was driven by empirical screening, but technological advances have lead to an increased focus on mechanism-based approaches to drug discovery and this is projected to increase as our capabilities advance to improve both the throughput of assays and the quality of data generated. Investment in the development of combination products with novel agents is increasing and, despite regulatory hurdles in some regions, efforts to globally harmonize regulations will aid in delivering safe, efficacious drugs to help in resistance management and integrated parasite control programs.

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Selective Drug Targets in Parasites

Cited by 3 publications

References 57 publications

Potential of recombinant inorganic pyrophosphatase antigen as a new vaccine candidate against Baylisascaris schroederi in mice

Potential of recombinant inorganic pyrophosphatase antigen as a new vaccine candidate against Baylisascaris schroederi in mice

Drug Discovery Approaches toward Anti‐Parasitic Agents

Discovery and Development of Veterinary Antiparasitic Drugs: Past, Present and Future

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