title: Development of a metabolically active, non-replicating sporozoite vaccine to prevent Plasmodium falciparum malaria.
abstract: Immunization of volunteers by the bite of mosquitoes carrying radiation-attenuated Plasmodium falciparum sporozoites protects greater than 90% of such volunteers against malaria, if adequate numbers of immunizing biting sessions and sporozoite-infected mosquitoes are used. Nonetheless, until recently it was considered impossible to develop, license and commercialize a live, whole parasite P. falciparum sporozoite (PfSPZ) vaccine. In 2003 Sanaria scientists reappraised the potential impact of a metabolically active, non-replicating PfSPZ vaccine, and outlined the challenges to producing such a vaccine. Six years later, significant progress has been made in overcoming these challenges. This progress has enabled the manufacture and release of multiple clinical lots of a 1(st) generation metabolically active, non-replicating PfSPZ vaccine, the Sanaria PfSPZ Vaccine, submission of a successful Investigational New Drug application to the US Food and Drug Administration, and initiation of safety, immunogenicity and protective efficacy studies in volunteers in MD, US. Efforts are now focused on how best to achieve submission of a successful Biologics License Application and introduce the vaccine to the primary target population of African children in the shortest possible period of time. This will require implementation of a systematic, efficient clinical development plan. Short term challenges include optimizing the (1) efficiency and scale up of the manufacturing process and quality control assays, (2) dosage regimen and method of administration, (3) potency of the vaccine, and (4) logistics of delivering the vaccine to those who need it most, and finalizing the methods for vaccine stabilization and attenuation. A medium term goal is to design and build a facility for manufacturing highly potent and stable vaccine for pivotal Phase 3 studies and commercial launch.
authors: Sanaria Inc., Rockville, MD, USA. slhoffman@sanaria.com
authors: Stephen L
authors: SL
authors: Hoffman
authors: Peter F
authors: PF
authors: Billingsley
authors: Eric
authors: E
authors: James
authors: Adam
authors: A
authors: Richman
authors: Mark
authors: M
authors: Loyevsky
authors: Tao
authors: T
authors: Li
authors: Sumana
authors: S
authors: Chakravarty
authors: Anusha
authors: A
authors: Gunasekera
authors: Rana
authors: R
authors: Chattopadhyay
authors: Minglin
authors: M
authors: Li
authors: Richard
authors: R
authors: Stafford
authors: Adriana
authors: A
authors: Ahumada
authors: Judith E
authors: JE
authors: Epstein
authors: Martha
authors: M
authors: Sedegah
authors: Sharina
authors: S
authors: Reyes
authors: Thomas L
authors: TL
authors: Richie
authors: Kirsten E
authors: KE
authors: Lyke
authors: Robert
authors: R
authors: Edelman
authors: Matthew B
authors: MB
authors: Laurens
authors: Christopher V
authors: CV
authors: Plowe
authors: B Kim Lee
authors: BK
authors: Sim
mesh_terms: D002986:Clinical Trials as Topic; D017277:Drug Approval; D006801:Humans; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D010963:Plasmodium falciparum / Q000276:immunology*; D034101:Sporozoites / Q000276:immunology*; D014481:United States; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D017780:Malaria Vaccines; D014613:Vaccines, Attenuated