Plasmodium falciparum 7G8 challenge provides conservative prediction of efficacy of PfNF54-based PfSPZ Vaccine in Africa.
AuthorSilva, Joana C
Moser, Kara A
Sissoko, Mahamadou S
Epstein, Judith E
Healy, Sara A
Lyke, Kirsten E
Kremsner, Peter G
Duffy, Patrick E
Sim, B Kim Lee
Richie, Thomas L
Hoffman, Stephen L
MetadataShow full item record
AbstractControlled human malaria infection (CHMI) has supported Plasmodium falciparum (Pf) malaria vaccine development by providing preliminary estimates of vaccine efficacy (VE). Because CHMIs generally use Pf strains similar to vaccine strains, VE against antigenically heterogeneous Pf in the field has been required to establish VE. We increased the stringency of CHMI by selecting a Brazilian isolate, Pf7G8, which is genetically distant from the West African parasite (PfNF54) in our PfSPZ vaccines. Using two regimens to identically immunize US and Malian adults, VE over 24 weeks in the field was as good as or better than VE against CHMI at 24 weeks in the US. To explain this finding, here we quantify differences in the genome, proteome, and predicted CD8 T cell epitopes of PfNF54 relative to 704 Pf isolates from Africa and Pf7G8. We show that Pf7G8 is more distant from PfNF54 than any African isolates tested. We propose VE against Pf7G8 CHMI for providing pivotal data for malaria vaccine licensure for travelers to Africa, and potentially for endemic populations, because the genetic distance of Pf7G8 from the Pf vaccine strain makes it a stringent surrogate for Pf parasites in Africa.
Data AvailibilityThe genome of the reference Pf 3D7 strain and respective structural annotation were obtained from PlasmoDB (release-24). All whole genome sequence datasets used in this study were downloaded through the NCBI’s Sequence Read Archive (SRA) database. Accession IDs are available in Supplementary Data 1. For the clinical trials17,28,34,35, the data supporting the findings of studies are available within the Articles and their Supplementary Information and from the corresponding authors upon reasonable request, and after execution of inter-institutional human data sharing agreements.; All computer programs used in the analysis of these data are referenced in the “Methods” section.
Rights/Terms© 2022. The Author(s).
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/19189
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