First-in-human evaluation of genetically attenuated Plasmodium falciparum sporozoites administered by bite of Anopheles mosquitoes to adult volunteers
Michele Spring, Jittawadee Murphy, Robin Nielse, Megan Dowler, Jason W Bennett, Stasya Zarling, Jack Williams, Patricia de la Vega, Lisa Ware, Jack Komisar, Mark Polhemus, Thomas L Richie, Judy Epstein, Cindy Tamminga, Ilin Chuang, Nancy Richie, Michael O'Neil, D Gray Heppner, Julie Healer, Matthew O'Neill Show all
VACCINE | ELSEVIER SCI LTD | Published : 2013
BACKGROUND: Immunization with genetically engineered, attenuated malaria parasites (GAP) that arrest during liver infection confers sterile protection in mouse malaria models. A first generation Plasmodium falciparum GAP (Pf p52(-)/p36(-) GAP) was previously generated by deletion of two pre-erythrocytic stage-expressed genes (P52 and P36) in the NF54 strain. METHODS: A first-in-human, proof-of-concept, safety and immunogenicity clinical trial in six human volunteers was conducted. Exposure consisted of delivery of Pf p52(-)/p36(-) GAP sporozoites via infected Anopheles mosquito bite with a five-bite/volunteer exposure followed by an approximately 200-bite exposure/volunteer one month later. ..View full abstract
The research was funded by a Grant from the Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative to SHIK and US Army Medical Research and Materiel Command. The opinions or assertions contained herein are the private views of the authors, and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. We would like to thank members of Statistics Collaborative, Inc. for their help with the study and Ashley M. Vaughan for editorial suggestions.