Anti-Pfs25 Human Plasma Reduces Transmission of Diverse Plasmodium falciparum

34 Pfs25 is a leading candidate for a malaria transmission blocking vaccine who’s potential has 35 been demonstrated in a Phase 1 trial with recombinant Pfs25 formulated with Montanide 36 ISA51. Because of limited sequence polymorphism, the anti-Pfs25 antibodies induced by this 37 vaccine are likely to have transmission blocking or reducing activity against most, if not all, field 38 isolates. To test this hypothesis, we evaluated transmission blocking activities by membrane 39 feeding assay of anti-Pfs25 plasma from the Pfs25/ISA51 Phase I trial, against P. falciparum 40 parasites from patients in two different geographical regions of the world, Thailand and Burkina 41 Faso. In parallel, parasite isolates from these patients were sequenced for Pfs25 gene and 42 genotyped for seven microsatellites. The results indicate that despite different genetic 43 backgrounds among parasites isolates, the Pfs25 sequences are highly conserved, with a single 44 non-synonymous nucleotide polymorphism detected in one of 41 patients in Thailand and 45 Burkina Faso. The anti-Pfs25 immune plasma had significantly higher transmission reducing 46 activity against parasite isolates from the two geographic regions than the non-immune controls 47 (P<0.0001). 48 on O cber 8, 2017 by gest http/iai.asm .rg/ D ow nladed fom