The potential for vaccines against scour worms of small ruminants

Britton, Collette; Emery, D.L.; McNeilly, Tom N.; Nisbet, Alasdair J.; Stear, M. J.

doi:10.1016/j.ijpara.2020.04.003

Cited by 29 publications

(24 citation statements)

References 214 publications

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“…Today, there are research activities, mainly in academia, to discover protective vaccine candidates [44,76,85]. The further advancement of the 'omics', together with the rise of deep data analyses in multiple fields and other technologically advanced tools, will, in the near future, enable next-generation vaccine development based on a profound understanding of the host-parasite interaction [86][87][88].…”

Section: Approaches To Antiparasitic Developmentmentioning

confidence: 99%

Antiparasitics in Animal Health: Quo Vadis?

Selzer

Epe

2021

Trends in Parasitology

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Antiparasitics acting on endo-or ectoparasites represent the second largest segment of the global animal health market, accounting for 23% of market share. However, relatively few novel antiparasitic agents have been introduced into the market during recent decades. One exception, and a groundbreaking 21st century success story, are the isoxazolines, whose full potential has not yet been entirely explored. Unfortunately, resistance issues are present across most parasitic diseases, which generates a clear market need for novel resistance-breaking antiparasitics with new modes/mechanisms of action. Recent advances in science and technologies strongly suggest that the time is right to invest in new modalities such as parasitic vaccines or in environmentally friendly interventions. The Animal Health IndustryAnimal health is focused on the management and control of diseases in order to ensure the health of both livestock (see Glossary) and companion animals. The global market for animal health products approaches €30 billion per year, with an annual growth rate outstripping that of human medicine. Products include biologicals (e.g., vaccines), antiparasitics/parasiticides, anti-infectives (e.g., antibiotics, antifungals), other pharmaceuticals (e.g., antihypertensives, antidiabetics), and medical feed additives (Figure 1, Key Figure). The current animal health market is understood to be driven primarily by three factors:(i) Pet owners, farmers, and veterinarians prefer more technically advanced and more convenient treatments. (ii) The growing world population increasingly demands affordable sources of protein from food animals and animal products, requiring improvements in livestock health care. (iii) The development of resistance requires new resistance-breaking preventatives and treatments.Due to the high economic impact and the immediate relevance for animal health, antiparasitics, also referred to as parasiticides, currently represent the second largest segment of the global animal health markettaking turns almost on a yearly basis with biologicals as the largest segmentaccounting for €7 billion in sales (23% of the market share) (Figures 1 and 2).In addition, animal health plays an important role in furthering the 'One Health' initiative, which is dedicated to improving the lives of all specieshuman and animalthrough the integration of human medicine, veterinary medicine, and environmental science i . The 'Antiparasitics Focus' of the Animal Health IndustryParasitic infections account for some of the most significant diseases worldwide, in both animals and humans, and are of enormous socioeconomic importance. Despite significant treatment advances in the preceding half century, they remain a major threat to livestock farming and cause large deficits for the agricultural economy. Effective parasite control is thus essential for profitability in intensive livestock production [1,2]. HighlightsAntiparasitics for the treatment of companion animals and livestock is one of the largest global market segments in the ani...

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Section: Approaches To Antiparasitic Developmentmentioning

confidence: 99%

Antiparasitics in Animal Health: Quo Vadis?

Selzer

Epe

2021

Trends in Parasitology

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“…However, numerous challenges need to be overcome in a continued effort to discover new compounds with enhanced performance (safety, efficacy and convenience), particularly given the ineffectiveness of some treatments and the widespread drug resistance in many parasites of many host species [ 1 , 2 ]. Although substantial efforts have gone into vaccine discovery and development, there is currently no licensed, safe and effective vaccine against a human helminthiasis, and only a very small number of vaccines have been approved for use in animals in some countries [ 3 , 4 , 5 , 6 , 7 , 8 ], with Barbervax ®® against haemonchosis in livestock being one relatively recent example [ 7 ]. While vaccination (immunoprophylaxis) would be the preferred option for prevention, vaccines against gastrointestinal worms may not achieve sufficiently high levels of protection for long enough periods to sustain the prevention/control of disease, such that strategic anthelmintic treatment or integrated strategies will still be required [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

High-Throughput Phenotypic Assay to Screen for Anthelmintic Activity on Haemonchus contortus

et al. 2021

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Parasitic worms cause very significant diseases in animals and humans worldwide, and their control is critical to enhance health, well-being and productivity. Due to widespread drug resistance in many parasitic worms of animals globally, there is a major, continuing demand for the discovery and development of anthelmintic drugs for use to control these worms. Here, we established a practical, cost-effective and semi-automated high throughput screening (HTS) assay, which relies on the measurement of motility of larvae of the barber’s pole worm (Haemonchus contortus) using infrared light-interference. Using this assay, we screened 80,500 small molecules and achieved a hit rate of 0.05%. We identified three small molecules that reproducibly inhibited larval motility and/or development (IC50 values of ~4 to 41 µM). Future work will critically assess the potential of selected hits as candidates for subsequent optimisation or repurposing against parasitic nematodes. This HTS assay has a major advantage over most previous assays in that it achieves a ≥ 10-times higher throughput (i.e., 10,000 compounds per week), and is thus suited to the screening of libraries of tens of thousands to hundreds of thousands of compounds for subsequent hit-to-lead optimisation or effective repurposing and development. The current assay should be adaptable to many socioeconomically important parasitic nematodes, including those that cause neglected tropical diseases (NTDs). This aspect is of relevance, given the goals of the World Health Organization (WHO) Roadmap for NTDs 2021–2030, to develop more effective drugs and drug combinations to improve patient outcomes and circumvent the ineffectiveness of some current anthelmintic drugs and possible drug resistance.

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“…For a vaccine study against H. contortus, adjuvant selection for vaccine antigens is tremendously crucial to augment and prolong vaccination-induced protective immunity (Britton et al, 2020). In the preliminary study, co-administration of candidate antigens with Freund's adjuvants has been shown to facilitate durable and robust cellular and humoral immunity against H. contortus challenge.…”

Section: Discussionmentioning

confidence: 99%

“…Since much research in the development of recombinant versions of promising native antigens has failed, recent vaccine studies have focused on the characterization of novel candidate antigens including their temporal/spatial expression profiles, immunomodulatory attributes, effective recombinant production and protective efficacy (Emery et al, 2016;Matthews et al, 2016;Nisbet et al, 2016). In addition to the exploitation of novel protective antigens, the development of cocktail vaccines containing multiple native or recombinant antigens with prophylactic potential might be a promising strategy (Nisbet et al, 2016;Noon and Aroian, 2017;Britton et al, 2020). The most persuasive laboratory data were provided by a vaccine study targeting T. circumcincta, reporting an immunization regime that incorporated eight recombinant T. circumcincta antigens.…”

Section: Discussionmentioning

confidence: 99%