New tools for NTD vaccines: A case study of quality control assays for product development of the human hookworm vaccine<i>Na</i>-APR-1<sub>M74</sub>

Pearson, Mark S.; Jariwala, Amar; Abbenante, Giovanni; Plieskatt, Jordan; Wilson, David T.; Bottazzi, María Elena; Hotez, Peter J.; Keegan, Brian; Bethony, Jeffrey M.; Loukas, Alex

doi:10.4161/21645515.2014.980199

Cited by 17 publications

(7 citation statements)

References 36 publications

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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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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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“…These results were explained by the mutant Na-APR-1 ability to trigger neutralizing antibodies to both the native enzyme (Na-APR-1) and APR-1 orthologs from the other three human hookworm species [158]. Na-APR-1 (M74) administered to mice as low as 0.99 μg could trigger specific antibodies (IgG), which inhibited 89% of the native protease enzymatic activity, supporting this mutant protein as a vaccine candidate [159]. Additionally, serum from a rabbit vaccinated with U. stenocephala aspartic protease (Us-APR-1) showed cross-reactivity with an aspartic protease from a heterologous dog hookworm species, A. ceylanicum (Ace-APR-1) [67].…”

Section: Targets For Vaccine and Therapymentioning

confidence: 91%

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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“…Kentucky BioProcessing and other tobacco growers, for example, are employing tobacco plants to express SARS-CoV-2 vaccine antigens [ 91 ]. While the manufacturing of recombinant proteins in tobacco is a proven technology [ [92] , [93] , [94] , [95] ], controlling cost at the pandemic scale might reserve this expression system to those with access to the necessary capacity.…”

Section: Protein Production Technologiesmentioning

confidence: 99%

Recombinant protein vaccines, a proven approach against coronavirus pandemics

Pollet

Chen

Strych

2021

Advanced Drug Delivery Reviews

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176

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New tools for NTD vaccines: A case study of quality control assays for product development of the human hookworm vaccineNa-APR-1_M74

Cited by 17 publications

References 36 publications

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

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

Recombinant protein vaccines, a proven approach against coronavirus pandemics

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New tools for NTD vaccines: A case study of quality control assays for product development of the human hookworm vaccineNa-APR-1M74

Cited by 17 publications

References 36 publications

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

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

Recombinant protein vaccines, a proven approach against coronavirus pandemics

Contact Info

Product

Resources

About

New tools for NTD vaccines: A case study of quality control assays for product development of the human hookworm vaccineNa-APR-1_M74