Lymphocyte depletion markedly decreased protection, suggesting a

Lymphocyte depletion markedly decreased protection, suggesting a primarily TH2-mediated immune response [Adler-Moore et al. 2011]. Listeriolysin Cytolysins are virulence factors of various pathogenic bacteria. They form pores

in target cell membranes, degrade membrane lipids or solubilize cell membranes. Bacteria use cytolysins order Ibrutinib to either inhibit functions of host immune cells or to gain access to intracellular niches. The bacterium Listeria monocytogenes can escape host immune defenses by lysis of the phagosomal membrane by use of listeriolysin O (LLO). LLO is used as vaccine adjuvant to provide cytosolic access for antigens in APCs [Dietrich et al. 2001]. LLO-based vaccines were reported by Mandal and Lee, who prepared OVA/LLO liposomes. OVA immunization resulted in higher CTL activity and high IFNγ production. The vaccine also conferred protection to mice from lethal challenges with

antigen-expressing tumor cells [Mandal and Lee, 2002]. LLO liposomes were also used to deliver the LCMV NP to stimulate a NP-specific CTL response. Immunized mice generated high frequencies of NP-specific CD8+ T cells and full protection against a lethal intracerebral challenge with virulent LCMV [Mandal et al. 2004]. An anionic liposome–polycation–DNA complex combined with LLO was used as vaccine by Sun and colleagues to deliver OVA-cDNA. This formulation produced an enhanced CD8+ T-cell response, higher CTL frequency and IFNγ production after stimulation by an OVA-specific peptide [Sun et al. 2010]. Andrews and colleagues analyzed whether encapsulating CpGs in LLO liposomes would enhance cell-mediated immune response and skew TH1-type responses in a protein antigen-based vaccine utilizing LLO liposomes. Coencapsulation of CpGs in LLO liposomes activated the nuclear factor κB pathway,

maintaining cytosolic delivery of antigen mediated by coencapsulated LLO. Immunization with OVA and CpG-LLO liposomes showed enhanced TH1 immune responses Brefeldin_A [Andrews et al. 2012]. Currently, 26 clinical trials are registered at ClinicalTrials.gov, a service of the US National Institutes of Health (see ClinicalTrials.gov with the search terms liposome AND vaccine). Veterinary vaccines Knowledge of molecular details of immune mechanisms is relatively scarce for veterinary and pet animals and special concerns regarding the use of vaccine adjuvants must be considered. Demands such as compatibility with human consumption, animal production, costs, challenges met by different species, vaccine administration for large numbers of animals and others must be evaluated [Heegaard et al. 2011; Underwood and Van Eps, 2012]. Table 2 summarizes some of the most recent experimental studies of liposome-based veterinary vaccines.

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