Document Type
Journal Article
Publication Date
2018
Journal
Open Forum Infectious Diseases
Volume
5
Issue
5
DOI
10.1093/ofid/ofy083
Abstract
Background
Controlled human hookworm infection (CHHI) is a central component of a proposed hookworm vaccination-challenge model (HVCM) to test the efficacy of candidate vaccines. Critical to CHHI is the manufacture of Necator americanus infective larvae (NaL3) according to current Good Manufacturing Practice (cGMP) and the determination of an inoculum of NaL3 that is safe and reliably induces patent infection. Methods
cGMP-grade NaL3 were produced for a phase 1 trial in 20 healthy, hookworm-naïve adults in the United States, who received either 25 or 50 NaL3. Participants were monitored for 12–18 weeks postinfection for safety, tolerability, and patency of N. americanusinfection. Results
Both NaL3 doses were well tolerated. Early manifestations of infection included pruritus, pain, and papulovesicular rash at the application site. Gastrointestinal symptoms and eosinophilia appeared after week 4 postinfection. The 50 NaL3 inoculum induced patent N. americanus infection in 90% of this dose group. Conclusions
The inoculum of 50 NaL3 was well tolerated and consistently induced patent N. americanus infection suitable for future HVCM trials. Clinical Trials Registration
NCT01940757.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
APA Citation
Diemert, D., Campbell, D., Brelsford, J., Leasure, C., Li, G., Younes, N., & +several additional authors (2018). Controlled Human Hookworm Infection: Accelerating Human Hookworm Vaccine Development. Open Forum Infectious Diseases, 5 (5). http://dx.doi.org/10.1093/ofid/ofy083
Peer Reviewed
1
Open Access
1
Included in
Medical Immunology Commons, Medical Microbiology Commons, Parasitic Diseases Commons, Parasitology Commons, Tropical Medicine Commons
Comments
Reproduced with permission of Oxford University Press. Open Forum Infectious Diseases