Development of a Current Good Manufacturing Practice–Compliant Process for Producing Cryptosporidium parvum Oocysts for Clinical Use
Year: 2026
Type: article
Abstract: BACKGROUND: Cryptosporidiosis is a leading cause of severe diarrhea and mortality in young children with no vaccine or effective treatment. Cryptosporidium controlled human infection model (CHIM) in healthy adults provides an opportunity to evaluate the safety and efficacy of novel chemical entities prior to testing in young pediatric patients. However, CHIM development has been hindered by the lack of current good manufacturing practice (cGMP)-compliant Cryptosporidium parvum oocysts, which are required for filing an Investigational New Drug Application (IND) with the U.S. Food and Drug Administration. METHODS: To overcome this barrier, we developed a cGMP-compliant process for producing C. parvum oocysts. The approach involved sourcing well-characterized oocysts purified from neonatal calves under controlled non-GMP conditions, followed by cGMP processing that included peracetic acid-based surface sanitization, comprehensive microbial testing and release as a non-sterile oral product for human use. RESULTS: Peracetic acid (0.5% for 20 minutes) treated C. parvum oocysts demonstrated acceptable microbial safety and preserved viability. Viability was assessed through oocyst excystation, HCT-8 cell infection and mouse infectivity studies. The cGMP produced C. parvum oocysts with stringent batch-release test criteria for quantity, purity, identity, potency and bioburden was released as ABO809 for clinical use under an IND. ABO809 was successfully used in human challenge studies, producing reliable infection and characteristic clinical symptoms in healthy adult volunteers. CONCLUSIONS: We describe a robust cGMP-compliant and qualification process for C. parvum oocysts that enables CHIM studies in healthy adults. Thereby opening avenues to evaluate efficacy of novel therapeutics and vaccines to treat cryptosporidiosis.
Authors: Rajiv S Jumani, Bryanna Thomas, Jay Lakshman, Christian Ostermeier, Natko Nuber, Juergen Hubert Blusch, Sofia Braud-Perez, Dean Wetty, Lizhuo Nouaime, Juergen Dederichs, Joseph Etse, Slobodan Grubesic, Suresh B Lakshminarayana, Lucy C Watson, Johanne Blais, Zachary Thompson, Tareq Z Jaber, Mark R Jones, Deborah A Schaefer, Michael W Riggs, Christopher D Huston, Thierry T Diagana, Ujjini H Manjunatha
Language: English
Subfield: Parasitology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,763
OpenAlex ID: W7130337417