Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 18, Issue -, Pages 414-425Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2018.11.005
Keywords
Vaccine; Ebola; Nanoparticle
Funding
- National Institutes of Health [R01AI127070, R01EB022563, R01HL125555]
- Defense Threat Reduction Agency [DTRACB3947]
- Melanoma Research Alliance [348774]
- DoD/CDMRP Peer Reviewed Cancer Research Program [W81XWH-16-1-0369]
- Emerald Foundation
- NSF CAREER Award [1553831]
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The recent outbreaks of Ebolavirus (EBOV) in West Africa underscore the urgent need to develop an effective EBOV vaccine. Here, we report the development of synthetic nanoparticles as a safe and highly immunogenic platform for vaccination against EBOV. We show that a large recombinant EBOV antigen (rGP) can be incorporated in a configurational manner into lipid-based nanoparticles, termed interbilayer-crosslinked multilamellar vesicles (ICMVs). The epitopes and quaternary structure of rGP were properly maintained on the surfaces of ICMVs formed either with or without nickel nitrilotriacetic acid (NTA)-functionalized lipids. When administered in mice. rGP-ICMVs without NTA-lipids efficiently generated germinal center B cells and polyfunctional T cells while eliciting robust neutralizing antibody responses. This study suggests the potential of vaccine nanoparticles as a delivery platform for configurational, multivalent display of large subunit antigens and induction of neutralizing antibody and T cell responses. (C) 2018 Elsevier Inc. All rights reserved.
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