A Nanolipoprotein Particle Platform Vaccine Targeting Ebola Virus Elicits a Robust Immune Response In Vivo 9334

Abstract Description The Ebola virus is a negative sense, single-stranded RNA virus that causes Ebola virus disease (EVD), with a fatality infection rate of approximately 50%. In 2019, the first FDA-approved vaccine was introduced and while effective, limitations remain. Here, we outline the development of a nanolipoprotein (NLP) vaccine delivery platform to evaluate an NLP-based Ebola vaccine by incorporating the Zaire Ebola virus glycoprotein (GP), combined with a cholesterol-tagged CpG 2006 adjuvant conjugated to the NLP (NLP:GP:CpG), with and without Alhydrogel (Alh). C57BL/6 were vaccinated intramuscularly (IM) using a prime-boost regimen four weeks apart. 10 days post-boost, blood and spleens were harvested to quantify humoral and cell-mediated responses. Animals vaccinated with NLP:GP:CpG and NLP:GP:CpG + Alh exhibited robust GP-specific IgG antibody titers with NLP:GP:CpG + Alh eliciting significant titers in the Pseudovirion neutralization assay relative to PBS controls. Notably, ELISpot analysis revealed significant antigen-specific IFNγ levels in splenocytes from animals vaccinated with NLP:GP:CpG, compared to PBS controls. Similarly, transcriptomic data of differentially expressed genes involved in T-cell and B-cell activation, showed distinct profiles between the Alh and non-Alh formulations. These findings suggest that the NLP is a promising alternative vaccine delivery platform for EBOV and underscores the impact of adjuvants/adjuvant combinations on shaping the immune response. Funding Sources DTRA: HDTRA1242031 Topic Categories Vaccines and Immunotherapy (VAC)