Immunization with OVA admixed with different liposomes generated different antibody responses. Interestingly, OVA admixed with negative 1,2-dioleyl-sn-glycero-3-phosphatidic acid liposomes was as immunogenic as OVA admixed with positive 1,2-dioleoyl-3-trimethyl

PARP signaling ammonium propane liposomes. The cOVA antigen showed comparable adjuvant activities in all liposomes [Yanasarn et al. 2011]. Neutral phosphatidylcholine (PC)/cholesterol small unilamellar vesicles (SUV) also proved to be effective vaccine carriers. We evaluated a vaccine with peptides derived from the glycoprotein of the lymphocytic choriomeningitis virus (LCMV). Liposome-encapsulated peptides were highly immunogenic and elicited protective antiviral immunity by in vivo antigen loading of DCs. Encapsulated cytosine–phosphorothioate–guanine oligodeoxynucleotides (CpGs) further enhanced immune activation [Ludewig et al. 2000]. We also used the vaccine to prime

a CD8+ T-cell response against 10 different hepatitis C virus (HCV) epitopes, resulting in strong CTL responses. Challenge experiments with Vaccinia virus expressing HCV epitopes emphasized the utility of neutral liposomes as HCV vaccine [Engler et al. 2004; Schwendener et al. 2010]. Moon and colleagues describe novel interbilayer-crosslinked multilamellar vesicles (MLVs) formed by crosslinking adjacent lipid bilayers within MLVs. These vesicles entrapped protein antigens in their core and lipid-based immunostimulatory molecules in the bilayers, forming a potent vaccine, eliciting strong T-cell and antibody responses [Moon et al. 2011]. Investigation of hemagglutinin (HA) adsorption versus encapsulation

and coencapsulation of CpGs in 3β-[N-(N’,N’-dimethylaminoethane)-carbamoyl] cholesterol (DC-chol) liposomes showed that adsorbed HA was more immunogenic than encapsulated HA. Cholesterol enhanced the adjuvant effect and CpG-loaded liposomes were highly efficient at enhancing HA-specific humoral responses [Barnier Quer et al. 2012, 2013]. Covalent attachment of protein antigens to nanocarriers can disrupt protein Brefeldin_A structure and mask epitopes, altering the antibody response. Watson and colleagues used metal chelation via nitrilotriacetic acid (NTA) to attach antigens to liposomes. OVA and a HIV-1 gp41 (N-MPR) peptide were attached via NTA or covalent linkage. Attachment of N-MPR, but not OVA, elicited stronger antibody responses than antigen admixed with liposomes and covalent attachment was superior to NTA-anchored antigens [Watson et al. 2011]. Mannose receptors (MRs) expressed on macrophages and APCs mediate endocytosis and cooperate in antigen capture and presentation. MRs recognize carbohydrate moieties of many pathogens. Thus, targeting of glycosylated antigens or carrier systems to MRs is a method to develop vaccines [Irache et al. 2008].