Efficient co-delivery of subunit antigens and immunomodulatory agents to antigen-presenting cells in lymphoid tissues is required for effective modulation of antigen-specific immune responses. Here we present two distinct lipid-based nanoparticle systems that generate cytotoxic CD8+ T lymphocyte (CTL) responses. The first vaccine platform system is termed interbilayer-crosslinked multilamellar vesicles (ICMVs) that were formed by fusing liposomes into multilamellar vesicles and subsequent crosslinking of adjacent lipid headgroups across lipid bilayers within multilamellar vesicles. To compare ICMVs to other conventional nanoparticle vaccines, we immunized C57Bl/6 mice with a model antigen, ovalbumin, formulated into ICMVs, rehydration vesicles, and poly(lactide-co-glycolide) acid nanoparticles (NPs). ICMVs elicited a significantly enhanced CTL response, compared with other two vaccine NPs. We also compared OVA-loaded ICMVs to conventional DC-based vaccines and OVA + CpG emulsified in Montanide. OVA-ICMV vaccination increased the frequency of OVA-specific CD8+ T cells by ~31-fold by d 7, compared with OVA-DC and OVA-CpG-Montanide (<b>Fig. 1</b>), demonstrating superiority of ICMVs to conventional DC-based vaccines and a strong experimental adjuvant system. The second vaccine delivery platform is based on synthetic high-density lipoprotein nanodiscs (sHDLs). We have used an ApoA-I mimetic peptide (ESP22) to formulate phospholipids into homogenous nanodiscs with the average diameter of 10 ± 2.3 nm. These nanodiscs effectively delivered MHC-I minimal epitope peptides and CpG to dLNs and mediated anti-tumoral CTL responses against established tumors. These results suggest that lipid-based nanoparticles are promising vaccine delivery systems.<br/><br/>This study was supported by the NIH grant 1K22AI097291-01 and by the National Center for Advancing Translational Sciences of the NIH under Award Number UL1TR000433.

Engineering lipid-based vaccine nanoparticles for modulation of immune responses

249th National Meeting (2015)

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