Modulation of cellular immune response against hepatitis C virus nonstructural protein 3 by cationic liposome encapsulated DNA immunization

Abstract

A vaccine strategy directed to increase Th1 cellular immune responses, particularly to hepatitis C virus (HCV) nonstructural protein 3 (NS3), has considerable potential to overcome the infection with HCV. DNA vaccination can induce both humoral and cellular immune responses, but it became apparent that the cellular uptake of naked DNA injected into muscle was not very efficient, as much of the DNA is degraded by interstitial nucleases before it reaches the nucleus for transcription. In this paper, cationic liposomes composed of different cationic lipids, such as dimethyl-dioctadecylammonium bromide (DDAB), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), or 1,2-dioleoyl-sn-glycerol-3-ethylphosphocholine (DOEPC), were used to improve DNA immunization in mice, and their efficiencies were compared. It was found that cationic liposome-mediated DNA immunization induced stronger HCV NS3-specific immune responses than immunization with naked DNA alone. Cationic liposomes composed of DDAB and equimolar of a neutral lipid, egg yolk phosphatidylcholine (EPC), induced the strongest antigen-specific Th1 type immune responses among the cationic liposome investigated, whereas the liposomes composed of 2 cationic lipids, DDAB and DOEPC, induced an antigen-specific Th2 type immune response. All cationic liposomes used in this study triggered high-level, nonspecific IL-12 production in mice, a feature important for the development of maximum Th1 immune responses. In conclusion, the cationic liposome-mediated gene delivery is a viable HCV vaccine strategy that should be further tested in the chimpanzee model. (HEPATOLOGY 2003;37: 452-460.)

gp63 in Stable Cationic Liposomes Confers Sustained Vaccine Immunity to Susceptible BALB/c Mice Infected withLeishmania donovani

“…(16,27,77). Induction of potent Th1 responses by cationic liposomes (5,24) is consistent with our findings that mice vaccinated with gp63 in liposomes exhibited striking enhancements of the frequency and production of IFN-␥ from CD4 ϩ T cells both before infectious challenge and at 10 days or 12 weeks after infectious challenge. Significant frequencies of antigen-specific CD8 ϩ IFN-␥ ϩ cells were demonstrable only in the protected mice challenged 12 weeks after vaccination, supporting the idea of the importance of CD8 ϩ T cells in mediating long-term immunity (16,53).…”

“…Cationic liposomes have been shown to markedly potentiate activation of immune response to plasmid DNA and oligonucleotides (24,75). More recently, the induction of cell-mediated immune response to poorly immunogenic protein and peptide antigens has been made possible through the use of positively charged liposome carriers (5,44).…”

Codon optimization and mRNA amplification effectively enhances the immunogenicity of the hepatitis C virus nonstructural 3/4A gene

“…With respect to the NS3 protein of HCV, which has been evaluated in many laboratories as a therapeutic vaccine candidate, 7,8,13,23,34,35 some important findings have recently been made. The NS3 protein has three enzymatic functions in the viral life cycle.…”

DiC14‐amidine cationic liposomes stimulate myeloid dendritic cells through Toll‐like receptor 4

“…They were also shown to stimulate humoral as well as cell-mediated immune responses and are therefore considered as potential adjuvants for protein-based or DNA-based vaccines [2][3][4][5][6][7]. In this context, we previously demonstrated that mice injected with diC14-amidine (3-tetradecylamino-tert-butyl-N-tetradecylpropionamidine) cationic liposomes combined with a recombinant allergen (Der p 1) developed a Th1-biased immune response and were protected against subsequent induction of a Th2-type allergen-specific response [8].…”