Controlled Human Hookworm Infection: Accelerating Human Hookworm Vaccine Development.

Area of Science:

• Parasitology
• Vaccinology
• Clinical Trials

Background:

• Controlled human hookworm infection (CHHI) is crucial for developing a hookworm vaccination-challenge model (HVCM).
• Manufacturing hookworm infective larvae (NaL3) under current Good Manufacturing Practice (cGMP) and establishing a safe, effective inoculum are critical for CHHI.
• Clinical trial NCT01940757 investigated NaL3 safety and efficacy.

Purpose of the Study:

• To assess the safety and tolerability of two different doses of cGMP-grade Necator americanus infective larvae (NaL3).
• To determine the optimal NaL3 inoculum for reliably inducing patent hookworm infection in a human challenge model.

Main Methods:

• Twenty healthy, hookworm-naïve adults received either 25 or 50 cGMP-grade NaL3.
• Participants were monitored for 12-18 weeks post-infection for safety, tolerability, and evidence of patent Necator americanus infection.

Main Results:

• Both 25 and 50 NaL3 doses were well tolerated, with localized skin reactions and later gastrointestinal symptoms and eosinophilia.
• The inoculum of 50 NaL3 induced patent Necator americanus infection in 90% of participants in that dose group.

Conclusions:

• A 50 NaL3 inoculum is safe, well-tolerated, and consistently induces patent hookworm infection.
• This dose is suitable for use in future hookworm vaccination-challenge model trials.