Expression, purification, and characterization of the<i>Necator americanus</i>aspartic protease-1 (<i>Na</i>-APR-1 (M74)) antigen, a component of the bivalent human hookworm vaccine

Seid, Christopher A.; Curti, Elena; Jones, R. Mark; Hudspeth, Elissa M.; Rezende, Wanderson; Pollet, Jeroen; Versteeg, Leroy; Pritchard, Sonya; Musiychuk, Konstantin; Yusibov, Vidadi; Hotez, Peter J.; Bottazzi, María Elena

doi:10.1080/21645515.2015.1036207

Cited by 33 publications

(20 citation statements)

References 34 publications

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“…The use of Nicotiana benthamiana as expression host has already been explored for the production of a hookworm vaccine antigen25. Glycoengineering in plants may provide an opening to accelerate the manufacturing of novel vaccines for humans and livestock.…”

Section: Resultsmentioning

confidence: 99%

Production and glyco-engineering of immunomodulatory helminth glycoproteins in plants

Wilbers

Westerhof

Noort

et al. 2017

Sci Rep

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Helminth parasites control host-immune responses by secreting immunomodulatory glycoproteins. Clinical trials and mouse model studies have demonstrated the potential of helminth-derived glycoproteins for the treatment of immune-related diseases, like allergies and autoimmune diseases. Studies are however hampered by the limited availability of native parasite-derived proteins. Moreover, recombinant protein production systems have thus far been unable to reconstitute helminth-like glycosylation essential for the functionality of some helminth glycoproteins. Here we exploited the flexibility of the N-glycosylation machinery of plants to reconstruct the helminth glycoproteins omega-1 and kappa-5, two major constituents of immunomodulatory Schistosoma mansoni soluble egg antigens. Fine-tuning transient co-expression of specific glycosyltransferases in Nicotiana benthamiana enabled the synthesis of Lewis X (LeX) and LDN/LDN-F glycan motifs as found on natural omega-1 and kappa-5, respectively. In vitro and in vivo evaluation of the introduction of native LeX motifs on plant-produced omega-1 confirmed that LeX on omega-1 contributes to the glycoprotein’s Th2-inducing properties. These data indicate that mimicking the complex carbohydrate structures of helminths in plants is a promising strategy to allow targeted evaluation of therapeutic glycoproteins for the treatment of inflammatory disorders. In addition, our results offer perspectives for the development of effective anti-helminthic vaccines by reconstructing native parasite glycoprotein antigens.

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Section: Resultsmentioning

confidence: 99%

Production and glyco-engineering of immunomodulatory helminth glycoproteins in plants

Wilbers

Westerhof

Noort

et al. 2017

Sci Rep

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“…The development plan is to produce a vaccine product that contains two recombinant antigens known as Na -GST-1[50] and Na -APR-1[51, 52] formulated on aluminum hydroxide adjuvant. Each antigen is undergoing separate testing in Phase 1 trials prior to combining them and evaluating the vaccine for its efficacy to prevent hookworm infection.…”

Section: Discussionmentioning

confidence: 99%

Modeling the economic and epidemiologic impact of hookworm vaccine and mass drug administration (MDA) in Brazil, a high transmission setting

Bartsch

Hotez

Hertenstein

et al. 2016

Vaccine

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Background Although mass drug administration (MDA) has helped reduce morbidity attributed to soil-transmitted helminth infections in children, its limitations for hookworm infection have motivated the development of a human hookworm vaccine to both improve morbidity control and ultimately help block hookworm transmission leading to elimination. However, the potential economic and epidemiologic impact of a preventive vaccine has not been fully evaluated. Methods We developed a dynamic compartment model coupled to a clinical and economics outcomes model representing both the human and hookworm populations in a high transmission region of Brazil. Experiments simulated different implementation scenarios of MDA and vaccination under varying circumstances. Results Considering only intervention costs, both annual MDA and vaccination were highly cost-effective (ICERs ≤$790/DALY averted) compared to no intervention, with vaccination resulting in lower incremental cost-effectiveness ratios (ICERs ≤$444/DALY averted). From the societal perspective, vaccination was economically dominant (i.e., less costly and more effective) than annual MDA in all tested scenarios, except when vaccination was less efficacious (20% efficacy, 5 year duration) and MDA coverage was 75%. Increasing the vaccine's duration of protection and efficacy, and including a booster injection in adulthood all increased the benefits of vaccination (i.e., resulted in lower hookworm prevalence, averted more disability-adjusted life years, and saved more costs). Assuming its target product profile, a pediatric hookworm vaccine drastically decreased hookworm prevalence in children to 14.6% after 20 years, compared to 57.2% with no intervention and 54.1% with MDA. The addition of a booster in adulthood further reduced the overall prevalence from 68.0% to 36.0%, nearly eliminated hookworm infection in children. Conclusion Using a human hookworm vaccine would be cost-effective and in many cases economically dominant, providing both health benefits and cost-savings. It could become a key technology in effecting control and elimination efforts for hookworm globally.

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“…Currently, a divalent human hookworm vaccine consisted of Na-GST-1 and Na-APR-1 (M74) is under establishment by the Sabin Vaccine Institute Product Development Partnership. Both single antigen vaccines are in Phase 1 trials [163].…”

Section: Targets For Vaccine and Therapymentioning

confidence: 99%

Twenty-five-year research progress in hookworm excretory/secretory products

et al. 2020

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Hookworm infection is a major public health problem that threatens about 500 million people throughout tropical areas of the world. Adult hookworms survive for many years in the host intestine, where they suck blood, causing iron deficiency anemia and malnutrition. Numerous molecules, named excretory/secretory (ES) products, are secreted by hookworm adults and/or larvae to aid in parasite survival and pathobiology. Although the molecular cloning and characterization of hookworm ES products began 25 years ago, the biological role and molecular nature of many of them are still unclear. Hookworm ES products, with distinct structures and functions, have been linked to many essential events in the disease pathogenesis. These events include host invasion and tissue migration, parasite nourishment and reproduction, and immune modulation. Several of these products represent promising vaccine targets for controlling hookworm disease and therapeutic targets for many inflammatory diseases. This review aims to summarize our present knowledge about hookworm ES products, including their role in parasite biology, host-parasite interactions, and as vaccine and pharmaceutical targets and to identify research gaps and future research directions in this field.

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Expression, purification, and characterization of theNecator americanusaspartic protease-1 (Na-APR-1 (M74)) antigen, a component of the bivalent human hookworm vaccine

Cited by 33 publications

References 34 publications

Production and glyco-engineering of immunomodulatory helminth glycoproteins in plants

Production and glyco-engineering of immunomodulatory helminth glycoproteins in plants

Modeling the economic and epidemiologic impact of hookworm vaccine and mass drug administration (MDA) in Brazil, a high transmission setting

Twenty-five-year research progress in hookworm excretory/secretory products

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