4.7 Article

Preclinical evaluations of Pfs25-EPA and Pfs230D1-EPA in AS01 for a vaccine to reduce malaria transmission

Journal

ISCIENCE
Volume 26, Issue 7, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.isci.2023.107192

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The malaria transmission-blocking vaccine candidates Pfs25-EPA and Pfs230D1-EPA target the sexual stage development of Plasmodium falciparum in mosquitoes, reducing mosquito infectivity. Pfs25-EPA has shown safety and immunogenicity in a phase 1 field trial, while Pfs230D1-EPA has exhibited superior activity in a phase 1 US trial and is now in phase 2 field trials. Further development aims to enhance the immunogenicity of these candidates for a vaccine to reduce malaria transmission, and GSK Adjuvant Systems offer a potential platform for this development. Preclinical evaluations of Pfs25-EPA and Pfs230D1-EPA nanoparticles with GSK platforms showed stable formulations and induced stronger immune responses compared to Alhydrogel formulations.
Malaria transmission-blocking vaccine candidates Pfs25-EPA and Pfs230D1-EPA target sexual stage development of Plasmodium falciparum parasites in the mosquito host, thereby reducing mosquito infectivity. When formulated on Alhydrogel, Pfs25-EPA has demonstrated safety and immunogenicity in a phase 1 field trial, while Pfs230D1-EPA has shown superior activity to Pfs25-EPA in a phase 1 US trial and has entered phase 2 field trials. Development continues to enhance immunogenicity of these candidates toward producing a vaccine to reduce malaria transmission (VRMT) with both pre-erythrocytic (i.e., anti-infection) and transmission-blocking components. GSK Adjuvant Systems have demonstrated successful potency in pre-erythrocytic vaccine trials and might offer a common platform for VRMT development. Here, we describe preclinical evaluations of Pfs25-EPA and Pfs230D1-EPA nanoparticles with GSK platforms. Formulations were stable after a series of assessments and induced superior antibody titers and functional activity in CD-1 mice, compared to Alhydrogel formulations of the same antigens.

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