Hookworm: "the great infection of mankind"

Abstract

Over the last five years, there has been increasing recognition of the global health importance of hookworm. New international efforts to control the morbidity of hookworm are in progress

Figure 1. Global Distribution of Human Hookworm Infection

(Illustration: Margaret Shear, Public Library of Science, adapted from [4])

Figure 2. The Relationship between Poverty and Hookworm Prevalence

(Illustration: Margaret Shear, Public Library of Science, adapted from [4])

Figure 3. Life Cycle of the Human Hookworm N. americanus

The BZA anthelminthics albendazole and mebendazole remove adult hookworms from the gastrointestinal tract. In contrast, the Na-ASP-2 Hoookworm Vaccine is designed to target third-stage infective larvae (filariform larvae). Humoral immunity to the vaccine inhibits the entry of larvae into the gastrointestinal tract and thereby prevents their development into blood-feeding adult parasites. (Illustration: Sapna Khandwala, Public Library of Science, adapted from [3] and [33])

Figure 4. Scheme for the Development and Quality-Control Testing of the Na-ASP-2 Hookworm Vaccine, and Its Transition from the Laboratory into the Clinic

After the selection of ASP-2 from N. americanus (Na-ASP-2) as the lead candidate antigen based on a series of research and development (R&D) tests—which included immunoepidemiology studies identifying human correlates of immunity to hookworm and confirmatory laboratory animal vaccine trials—the recombinant antigen was expressed in yeast and then developed as a biologic through a well-defined product development strategy (PDS). By following the product development strategy, process development (PD) and manufacturing led to the generation of pilot batches at different scales prior to technology transfer to a cGMP manufacturing facility. Both process development and manufacturing rely on developing assays for the product's identity, color and appearance, purity, immunological recognition, and potency, as well as qualification of the assays for sensitivity, specificity, accuracy, and reproducibility. Each of these processes must maintain a high level of quality control by following a set of policies, protocols, and standard operating procedures. After the manufacturing of a cGMP product and the required pre-clinical animal testing, a clinical development plan (CDP) was generated. Because the Na-ASP-2 Hookworm Vaccine is a product destined for the world's poorest, it is being developed almost exclusively in the non-profit sector, along with government manufacturers in middle-income countries.