Abstract
An anti-malarial transmission blocking vaccine (TBV) would be an important tool for disease control or elimination, though current candidates have failed to induce high efficacy in clinical studies. The ookinete surface protein P25 is a primary target for TBV development, but heterologous expression of P25 with appropriate conformation is problematic and a pre-requisite for achieving functional titers. A potential alternative to recombinant/sub-unit vaccine is immunization with a non-pathogenic, whole-parasite vaccine. This study examines the ability of a purified transgenic rodent-malaria parasite (PbPfs25DR3), expressing Plasmodium falciparum P25 in native conformation on the P. berghei ookinete surface, to act as a TBV. Vaccination with purified PbPfs25DR3 ookinetes produces a potent anti-Pfs25 response and high transmission-blocking efficacy in the laboratory, findings that are then translated to experimentation on natural field isolates of P. falciparum from infected individuals in Burkina Faso. Efficacy is demonstrated in the lab and the field (up to 93.3%/97.1% reductions in transmission intensity respectively), with both a homologous strategy with one and two boosts, and as part of a prime-boost regime, providing support for the future development of a whole-parasite TBV.
Highlights
London, Norfolk Place, London, W2 1PG, UK
We demonstrate that immunization with purified PbPfs25DR3 ookinetes elicits a potent anti-Pfs[25] immune response, inducing antibodies that recognize native protein on the ookinete surface
We demonstrate that PbPfs25DR3 immunization can initiate an anti-malarial transmission-blocking response with high efficacy, both in vivo in immunized mice, and by direct membrane feeding assay (DMFA), ex vivo at a range of infection densities, on blood samples from infected African blood donors
Summary
ChAd63 (chimpanzee adenovirus 63) has been used to express Pfs[25] (and other TBVs previously), and when administered in a heterologous prime-boost regime, has elicited anti- parasitic moieties that are capable of blocking transmission in membrane-feeding assays[16,17] Using these systems, we demonstrate that immunization with purified PbPfs25DR3 ookinetes elicits a potent anti-Pfs[25] immune response, inducing antibodies that recognize native protein on the ookinete surface. We demonstrate that PbPfs25DR3 immunization can initiate an anti-malarial transmission-blocking response with high efficacy, both in vivo in immunized mice, and by direct membrane feeding assay (DMFA), ex vivo at a range of infection densities, on blood samples from infected African blood donors This data provides support for the future potential development of a whole-parasite TBV
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