<i>Plasmodium falciparum</i>mRNA liver stage antigens induce antibody and liver CD8 TRM and CD8 T Ecell responses in mice

Abstract Plasmodium spp. cause more than half a million malaria deaths annually and the only approved vaccine, RTS,S, based on P.falciparum (Pf) circumsporozoite protein (CSP), confers incomplete non-durable protection. A strategy to improve vaccines involves combining Ags of different stages such as sporozoite (spz) liver stage (LS). This promises broader repertoire specific antibodies (Ab), CD4 CD8 T cells. We have shown that mice immunized with combination P. berghei (Pb) CSP LS expressed DNA-Adenovirus generate higher protection alone. Protection is associated Ag-specific Abs RMcells. hypothesized spz escaped CSP-specific were targeted by LS-Ag-specific responses. Our current efforts are directed towards utilizing mRNA template it can accommodate many Ags. designed mRNA-LNP expressing single Pf-LS Ags, 305w SHMT, protective rodent parasite Ag orthologues, for immunization mice. Analyses mRNA-Pf-305w- Pf-SHMT-induced immune responses show divergence reactivities. Whereas Pf-305w induced high Ab titers, Pf-SHMT RMand Ecells exceeded Pf-305w-induced Peptides corresponding recalled IFN-g responses, signature immunity. continue characterize evaluate contributions cell B combinations including Pf-CSP immunity against transgenic parasites. provide rapid, flexible platform explore vaccine improvements where Ecells, cells may be crucial highly efficacious protracted