Manufacture of Necator americanus as an infectious challenge agent: Accelerating human hookworm vaccine development

Guacyara Erwin, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, 20052, United States of America.
Larissa Scholte, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, 20052, United States of America.
Rafaela Saes, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, 20052, United States of America.
Guangzhao Li, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, 20052, United States of America.
Linda Schellhaas, Quality Reviews, Inc., Falling Waters, WV, 25419, United States of America.
Ramesh Ratnappan, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, 20052, United States of America.
David I. Pritchard, School of Pharmacy, University of Nottingham, Boots Sciences Building, University Park, Nottingham, NG7 2RD, UK.
John Hawdon, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, 20052, United States of America.
David Diemert, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, 20052, United States of America; Department of Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, 20052, United States of America.
Jeffrey M. Bethony, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, 20052, United States of America. Electronic address: jbethony@gwu.edu.

Document Type

Journal Article

Publication Date

4-15-2025

Journal

Microbial pathogenesis

Volume

204

DOI

10.1016/j.micpath.2025.107592

Abstract

Hookworms infect 450 million people globally and account for the loss of 5 million disability-adjusted life years annually. Over the last decade, the Human Hookworm Vaccine (HHV) candidate N. americanus Glutathione-S-Transferase-1 (Na-GST-1) has advanced to efficacy testing. This manuscript describes the manufacture of third-stage N. americanus larvae (NaL3) as an infectious challenge agent to provide "proof-of-concept" for the efficacy of Na-GST-1 prior to more extensive and more resource-intensive vaccine field trials in hookworm endemic areas. NaL3 were produced from fecal samples of three hookworm-infected human donors by a modified Harada and Mori method that complied with current Good Manufacturing Practices (cGMP). A series of lot release tests assessed the purity (bioburden), viability (potency), and identity (speciation) of NaL3 before administration to participants in a hookworm vaccine challenge model (HVCM) in Washington, DC. Twenty-four production runs yielded an average of 947 NaL3 per lot, which were approved for clinical to inoculate of 39 participants in a Hookworm Vaccine Challenge Model. This manuscript describes the unique manufacture and testing for NaL3 in compliance with cGMP.

Department

Microbiology, Immunology, and Tropical Medicine

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