Design considerations for liposomal vaccines: influence of formulation parameters on antibody and cell-mediated immune responses to liposome associated antigens |
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Authors: | Watson Douglas S Endsley Aaron N Huang Leaf |
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Affiliation: | Biosciences Division, SRI International, 140 Research Drive, Harrisonburg, VA 22802, United States. watson.douglas@gmail.com [corrected]. |
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Abstract: | Liposomes (phospholipid bilayer vesicles) are versatile and robust delivery systems for induction of antibody and T lymphocyte responses to associated subunit antigens. In the last 15 years, liposome vaccine technology has matured and now several vaccines containing liposome-based adjuvants have been approved for human use or have reached late stages of clinical evaluation. Given the intensifying interest in liposome-based vaccines, it is important to understand precisely how liposomes interact with the immune system and stimulate immunity. It has become clear that the physicochemical properties of liposomal vaccines - method of antigen attachment, lipid composition, bilayer fluidity, particle charge, and other properties - exert dramatic effects on the resulting immune response. Here, we present a comprehensive review of the physicochemical properties of liposomal vaccines and how they influence immune responses. A discussion of novel and emerging immunomodulators that are suitable for inclusion in liposomal vaccines is also presented. Through a comprehensive analysis of the body of liposomal vaccine literature, we enumerate a series of principles that can guide the rational design of liposomal vaccines to elicit immune responses of a desired magnitude and quality. We also identify major unanswered questions in the field, pointing the direction for future study. |
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Keywords: | 111In-DTPA, 111In-labeled diethylenetriaminepentaacetic acid APC, antigen presenting cell ATRA, all-trans retinoic acid BCR, B cell receptor BSA, bovine serum albumin CCS, ceramide carbamoyl-spermine Chol, cholesterol CLR, C-type lectin receptor CpG, unmethylated cytosine-phosphate-guanine motifs CTL, cytotoxic T lymphocyte DC-Chol, 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl]cholesterol DC-SIGN, dendritic cell-specific intracellular adhesion molecule-3-grabbing non-integrin DCP, dicetylphosphate DDA, dimethyldioctadecylammonium DLiPC, 1,2-dilinoleoyl-sn-glycero-3-phosphocholine DLPC, 1,2-dilauryl-sn-glycero-3-phosphocholine DMPC, 1,2-dimyristoyl-sn-glycero-3-phosphocholine DNP, dinitrophenyl DNP-Cap-PE, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[6-[(2,4-dinitrophenyl)amino]hexanoyl] DOPC, 1,2-dioleoyl-sn-glycero-3-phosphocholine DOTAP, 1,2-dioleoyl-3-trimethylammonium propane DOTIM, 1-[2-(oleoyloxy)ethyl]-2-oleyl-3-(2-hydroxyethyl)imidazolinium DPPC, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine DPPE, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine DPyPE, 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine DRV, dehydration-rehydration vesicle DSPC, 1,2-distearoyl-sn-glycero-3-phosphocholine DSS, disuccinimidyl suberate DTH, Delayed-type hypersensitivity EMCS, N-(?-Maleimidocaproyloxy)succinimide EPC, 1,2-diacyl-sn-glycero-3-phosphocholine from egg EPG, 1,2-diacyl-sn-glycero-3-phosphoglycerol from egg ER, Endoplasmic reticulum GAP-DMORIE, N-(3-aminopropyl)-N,N-dimethyl-2,3-bis(cis-9-tetradeceneyloxy)-1-propanaminium GCSA, gross cell surface antigen GMS, glyceryl monostearate IFN-γ, interferon gamma IL-12, interleukin 12 LPA, Lysophosphatidic acid LPC, lysophosphatidylcholine LPD, lipid–protamine–DNA nanoparticle LPS, lipopolysaccharide MDP, muramyl dipeptide MHC, major histocompatibility complex MLV, multilamellar vesicle MPG, 2-monopalmitoylglycerol MPL, monophosphoryl lipid A NLR, NOD-like receptor NTA, nitrilotriacetic acid ODA, octadecanoic acid OVA, ovalbumin PA, palmitic acid PC, 1,2-diacyl-sn-glycero-3-phosphocholine PEG, poly(ethylene glycol) PG, 1,2-diacyl-sn-glycero-3-phosphoglycerol PLiPC, 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine poly(I:C), polyinosinic:polycytidylic acid PRR, pattern recognition receptor PS, 1,2-diacyl-sn-glycero-3-phosphoserine QS21, Quillaja saponaria Molina saponin REV, reverse phase evaporation vesicle SA, stearylamine SMS, sorbitan monostearate SP1, sphingosine-1-phosphate T20, Polyoxyethylene(20) sorbitan monolaurate SPDP, (N-succinimidyl-3-(2-pyridyldithio)-propionate) TAP, transporter associated with antigen processing TDB, α,α-trehalose-6,6′-dibehenate TGF-β, transforming growth factor beta TH1, T helper type 1 TH17, T helper type 17 TH2, T helper type 2 TH9, T helper type 9 TLR, Toll-like receptor Treg, T regulatory |
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