Malaria Vaccines: Pfs25-rEPA and Pfs230-rEPA

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

The major challenge facing TBV development is to find a highly safe formulation that induces sustained high antibody responses. LMIV has demonstrated that conjugating Pfs25 and Pfs230 with carrier protein ExoProtein A (EPA) of Pseudomonas aeruginosa greatly enhances the immunogenicity of the recombinant TBVs and has shown to be safe with the adjuvant Alhydrogel, but may need a stronger adjuvant such as AS01 to achieve the antibody responses needed to block transmission. Highlighted in this years summary are results from our publications in FY2022: 1. Duffy PE. The virtues and vices of Pfs230from vaccine concept to vaccine candidate. 2022. AJTMH. Jul 11 A Pfs230-based vaccine developed at LMIV is currently the target of the most advanced candidate for a malaria transmission-blocking vaccine. First identified by its orthologue in the avian malaria parasite Plasmodium gallinaceum, the large cysteine-rich 14-domain Pfs230 antigen is displayed on the surface of gametes that emerge in the mosquito midgut. Gametes lacking Pfs230 cannot bind to red blood cells nor develop further into oocysts. Human antibodies generated against Pfs230-D1 vaccine lyse gametes in the presence of complement, which largely explains serum transmission-blocking activity in Pfs230 antisera. A proteinprotein conjugate vaccine that incorporates the first domain of the Pfs230 antigen, Pfs230D1-EPA induced greater serum transmission-reducing activity versus a similarly manufactured Pfs25 vaccine in U.S. trials, establishing Pfs230D1-EPA as the worlds leading transmission-blocking vaccine candidate. Pfs230D1-EPA recently completed a phase II field trial in Mali. In addition to this publication, we have seen progress in our trials of Pfs25 and Pfs230 vaccines, listed below under these protocol titles: NIAID protocol 17-I-N006 Pfs230D1M-EPA/AS01 and Pfs25M-EPA/AS01 in Healthy Malian Adults NIAID protocol 19-I-N086: Safety, Immunogenicity and Efficacy of Pfs230D1M-EPA/AS01 Vaccine, a Transmission Blocking Vaccine against Plasmodium falciparum, in an Age De-Escalation Trial of Children and a Family Compound Trial in Mali FMPOS Protocol Number: 2021/210/CE/USTTB: Phase 1, Dose-Escalating, Double-Blind, Randomized, Comparator-Controlled Trial of the Safety, Tolerability, and Immunogenicity of the Transmission-Blocking Vaccine Pfs230D1EPA/Matrix-M against Plasmodium falciparum in Adults in Mali We are currently closing datasets for both trials 17-I-N006 and 19-I-N086 with planned publications in FY 2023. Trial 2021/210/CE/USTTB continues clinical follow up of subjects who received Pfs230D1EPA/Matrix-M in this first-in-human trial.