Development of malaria vaccines using the sail eRNATM platform 3618

Abstract Description Endless RNA™ (eRNA) has emerged as a promising platform for vaccines due to its circular format and extended half-life compared with traditional mRNA. In this study, 50 eRNA malaria vaccine constructs were designed using state-of-the-art artificial intelligence algorithms to express the same protein sequence used in licensed vaccines (R21 and RTSS: truncated Pf circumsporozoite protein (PfCSP) fused with HbS Ag). All eRNAs were expressed at high levels in HEK293 cells, and were exported and assembled into virus-like particles. Five sequence-optimized eRNA constructs were selected for in vivo immunogenicity testing in mice, and in an initial dose-finding study, eRNA vaccinations induced up to 24-fold higher anti-PfCSP IgG antibody titers, and 52-fold greater anti-NANP IgG antibody titers than the full-length PfCSP protein comparator. Additionally, titers remained elevated for up to 10 weeks after vaccinations. Furthermore, eRNA vaccinations elicited significantly higher anti-PfCSP IgM and IgA antibodies than protein vaccinations. eRNA performance was confirmed in a malaria vaccine reference laboratory where anti-PfCSP antibody titers were significantly greater for four of the five R21 eRNA vaccines than those reported for licensed malaria vaccines. These results demonstrate the potential of Sail’s eRNA platform to generate a scalable vaccine for malaria, with superior efficacy and durability than first-generation vaccines. Funding Sources Funding provided by Bill and Melinda Gates Foundation. Topic Categories Vaccines and Immunotherapy (VAC)