Lipid nanoparticles incorporated with Ebola glycoprotein for induction of humoral immunity against Ebola infection.

Abstract

Abstract The recent outbreaks of Ebola virus in Africa and isolated incidents in the U.S. have increased global attention and concern for this pathogen. The highly contagious nature and severe mortality rate of Ebola infection highlight the urgent need for an effective vaccine. To cull its spread, many vaccines are currently being tested in pre-clinical and clinical settings. Here, we report the development of a vaccine nanoparticle system that can safely elicit antibody responses and protect animals against Ebola viral challenge. We incorporated Ebola glycoprotein (GP) into lipid-based nanoparticles, called Interbilayer-crosslinked multilamellar vesicles (ICMVs), that were produced by fusing and crosslinking functionalized phospholipids. The resulting nanoparticles exhibited GP loading efficiency of 45–60 % with the particle diameter of approximately 350 nm. We observed strong binding of the murine mAbs 6D8 and 13C6, recognizing GP epitopes, on GP-ICMVs, indicating surface-bound GP in its natural configuration on ICMVs. C57BL/6 mice were immunized on days 0 and 21with 10 ug GP plus 2.5 ug monophosphoryl lipid A, a Toll-like receptor 4 agonist, in either ICMV or soluble formulations. Compared with the soluble GP+MPLA control, GP-ICMVs elicited 10-fold and 3-fold higher GP-specific IgG sera titers at two weeks post prime and boost, respectively. Vaccinated mice were challenged with 1000 p.f.u. of mouse adapted Ebola virus on day 28 after vaccination. All mice immunized with ICMVs survived up to 21 days post challenge, compared with 60 % survival for mice immunized with the GP+MPLA formulation. These preliminary experiments show strong elicitation of protective immunity however more research is needed to determine real world efficacy.