Rational selection of Toll-like receptor agonists (TLR) for the development of Marburg vaccine formulation

CPI RNA Vaccines 2023 -- Marburg virus infection causes haemorrhagic fever with fatality rates of up to 88%. Provision of a vaccine to Marburg virus is an unmet medical need. In response, a vaccine comprising a self-amplifying messenger RNA (sa mRNA) for the Marburg Glycoprotein (MARV GP) antigen, encapsulated in a lipid nanoparticle (LNP), is in development. As a further development, we are investigating incorporating Toll-like receptor (TLR) adjuvants into the MARV GP sa mRNA-LNPs to enhance the immune response. TLRs recognize microbial pathogen-associated molecular patterns (PAMPs) and activate the innate immune response; consequently, they can act as vaccine adjuvants. In this study, we investigate formulating MARV GP sa mRNA-LNPs with two TLR7 agonist variants, which are known to enhance immune responses to viral pathogens. More specifically, we have evaluated formulations with the small molecule TLR7 imidazoquinoline agonist Resiquimod (R848) and an alkylated variant Telratolimod. A design of experiment (DoE) approach has been used to select an optimised formulation to evaluate TLR7 enhancement of MARV GP sa RNA-LNP vaccine potency.