Immunologic aspects of liposomes: presentation and processing of liposomal protein and phospholipid antigens

Alving, Carl R.

doi:10.1016/0304-4157(92)90004-t

Cited by 106 publications

(38 citation statements)

References 124 publications

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“…In the absence of encapsulated or surface-coupled proteins, SSL and other nonviral lipid delivery systems are generally considered to be nonimmunogenic (van Rooijen and van Nieuwmegen, 1980;Alving, 1992;Harding et al, 1997). The immunogenicity and rapid plasma elimination of protein-coupled liposomal systems after repeat injections have been well documented (Aragnol and Leserman, 1986;Phillips and Emili, 1991;Phillips and Dahman, 1995;Harding et al, 1997;Tardi et al, 1997) and typically result from antibodymediated recognition of protein.…”

mentioning

confidence: 99%

Immunogenicity and Rapid Blood Clearance of Liposomes Containing Polyethylene Glycol-Lipid Conjugates and Nucleic Acid

Semple¹,

Harasym²,

Clow³

et al. 2004

J Pharmacol Exp Ther

185

131

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Polyethylene glycol (PEG) is used widely in the pharmaceutical industry to improve the pharmacokinetics and reduce the immunogenicity of therapeutic and diagnostic agents. The incorporation of lipid-conjugated PEG into liposomal drug delivery systems greatly enhances the circulation times of liposomes by providing a protective, steric barrier against interactions with plasma proteins and cells. Here we report that liposome compositions containing PEG-lipid derivatives and encapsulated antisense oligodeoxynucleotide (ODN) or plasmid DNA elicit a strong immune response that results in the rapid blood clearance of subsequent doses in mice. The magnitude of this response is sufficient to induce significant morbidity and, in some instances, mortality. This effect has been observed in several strains of mice and was independent of sequence motifs, such as immunostimulatory CpG motifs. The ODN-to-lipid ratio and ODN dose was also determined to be important, with abrogation of the response occurring at a ratio between 0.04 and 0.08 (w/w). Rapid elimination of liposome-encapsulated ODN from blood depends on the presence of PEG-lipid in the membrane because the use of nonpegylated liposomes or liposomes containing rapidly exchangeable PEG-lipid also abrogated the response. These studies have important implications for the evaluation and therapeutic use of liposomal formulations of nucleic acid, as well as the potential development of liposomal vaccines.

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mentioning

confidence: 99%

Immunogenicity and Rapid Blood Clearance of Liposomes Containing Polyethylene Glycol-Lipid Conjugates and Nucleic Acid

Semple¹,

Harasym²,

Clow³

et al. 2004

J Pharmacol Exp Ther

185

131

View full text Add to dashboard Cite

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“…3). The lack of a potentiating effect of the studied liposomal formulations in comparison with free antigens on the systemic immune response following immunization was not surprising based on previous studies [34][35][36]. Therefore, our findings as well as those of others demonstrate that the adjuvantic properties of liposomes strictly depend on their lipid composition and may be leveled in the presence of neutral phospholipids such as phosphatidylocholine.…”

Section: Discussionmentioning

confidence: 56%

The immunogenicity of the liposome-associated outer membrane proteins (OMPs) of Moraxella catarrhalis

Augustyniak¹,

Mleczko²,

Gutowicz³

2010

Cellular and Molecular Biology Letters

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The outer membrane proteins (OMPs) are the most immunogenic and attractive of the Moraxella catarrhalis vaccine antigens that may induce the protective immune response. The aim of this study was to determine the effectiveness of two types of OMP-associated phosphatidylcholine (PC) liposomal formulations (OMPs-PC, PC-OMPs) and of Zwittergent-based proteomicelles (OMPs-Z) in potentiating an anti-OMP systemic immune response in mice. The immunogenicities of the above preparations were evaluated by assessing serum anti-OMP IgG and IgA reactivity in the post-immunized mouse antisera using ELISA and Western blotting. Additionally, the cross-reactivity of the most effective anti-OMP response was determined using heterologous sera from both humans and mice. Both the proteoliposomes and the proteomicelles showed high immunogenic properties and did not elicit any distinct quantitative differences in the antibody titer or qualitative differences in the pattern of the mouse antisera. The post-immunized mouse antisera predominantly recognized a ∼60-kDa OMP of M. catarrhalis. That protein was also found to be a highly cross-reactive antigen interacting with a panel of pooled mouse antisera produced by immunization either with whole cells or the purified OMPs of heterologous M. catarrhalis strains. Furthermore, normal sera collected from healthy children were found to be preferentially reactive with the 60-kDa OMP. The serum-specific IgG, IgA and IgM were respectively detected via immunoblotting in 90%, 85% and 30% of heterologous human sera. This similar immunogenic effectiveness of both OMP-associated liposomal formulations could contribute to the practical use of such formulations in the future in human vaccination. Moreover, the highly cross-reactive 60-kDa OMP seems to be an important antigenic marker of M. catarrhalis, and, as it is responsible for the induction of an antibody-mediated and long-lasting immune response, studying it may partially aid us in understanding the relatively low degree of pathogenicity of the bacterium in immunocompetent individuals.

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“…After subcutaneous injection of mimovirus, this kind of particle might be easily internalized via the endocytosis pathway by the resident cells, especially professional APCs (3,36). This might be due to not only its particulate nature (2,8,18,22,28,35,38), with the size equivalent to a virus, but also its abundant cationic charges which help mimo- virus bind electrostatically to the overall negatively charged cell surface (14,17). Several studies have shown that DCs, macrophages, and even B cells were able to cross-present antigens under specific circumstances at least in vitro (1,3,9,12,15,16,23,27,29).…”

Section: Discussionmentioning

confidence: 99%

Mimovirus: a Novel Form of Vaccine That Induces Hepatitis B Virus-Specific Cytotoxic T-Lymphocyte Responses In Vivo

Zhao

Wan

et al. 2002

J Virol

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CD8؉ cytotoxic T lymphocytes (CTLs) are now recognized as important mediators of immunity against intracellular pathogens, including human immunodeficiency virus and tumors. How to efficiently evoke antigen-specific CTL responses in vivo has become a crucial problem in the development of modern vaccines. Here, we developed a completely novel CTL vaccine-mimovirus, which is a kind of virus-size particulate antigen delivery system. It was formed by the self-assembly of a cationic peptide containing 18 lysines and a CTLepitope peptide of HBsAg 28-39 , with a plasmid encoding mouse interleukin-12 (IL-12) through electrostatic interactions. We examined the formation of mimovirus by DNA retardation assay, DNase I protection assay, and transmission electron microscopy and demonstrated that mimovirus could efficiently transfer the plasmid encoding IL-12 into mammalian cells such as P815 cells in vitro. Furthermore, it was proved that mimovirus could induce an HBsAg 28-39 -specific CTL response in vivo. Considering its effectiveness, flexibility, and defined composition, mimovirus is potentially a novel system for vaccination against intracellular pathogens and tumors. CD8ϩ cytotoxic T lymphocytes (CTLs) play a key role in the immunity against tumors and intracellular pathogens including human immunodeficiency virus. Recent investigations have indicated that the key to eliciting CTL responses is to efficiently deliver antigens into the major histocompatibility complex class I (MHC-I) processing pathway of professional antigenpresenting cells (APCs), especially dendritic cells (DCs), which can thereby display high numbers of the MHC-I-peptide complexes in a rich costimulatory context to prime the specific naïve CD8 ϩ T cells (25,26,30,33). For this purpose, several particulate antigen delivery systems, such as immune-stimulating complexes (35), liposomes (2), virus-like particles (18), microspheres (22), and phage-displayed particles (8, 38), have been proved to be efficient. In addition, it has been suggested that coadministration of antigen with cytokines or other immunoregulatory molecules, either in the form of recombinant proteins or plasmids, could profoundly enhance immunity (25,30,33). Among them, interleukin-12 (IL-12) has been shown to be potent to promote the induction of CTL responses in vivo (6).Synthetic peptides corresponding to epitopes recognized by CTLs have been investigated as the basis of safe, effective vaccines (5). The cationic peptides represent a kind of synthetic DNA delivery system that is gaining increasing prominence in gene therapy (11,19,24,37). These cationic peptides (e.g., oligolysine, [K] n ) can bind to plasmid DNA through electrostatic interactions between the positively charged lysine residues and the negatively charged phosphate backbone of the DNA. This interaction forms highly condensed particles that protect the packaged DNA from the effects of nucleases and allow internalization by mammalian cells. Here, rationally combining the epitope-based peptide vaccine and the cationicpept...

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Immunologic aspects of liposomes: presentation and processing of liposomal protein and phospholipid antigens

Cited by 106 publications

References 124 publications

Immunogenicity and Rapid Blood Clearance of Liposomes Containing Polyethylene Glycol-Lipid Conjugates and Nucleic Acid

Immunogenicity and Rapid Blood Clearance of Liposomes Containing Polyethylene Glycol-Lipid Conjugates and Nucleic Acid

The immunogenicity of the liposome-associated outer membrane proteins (OMPs) of Moraxella catarrhalis

Mimovirus: a Novel Form of Vaccine That Induces Hepatitis B Virus-Specific Cytotoxic T-Lymphocyte Responses In Vivo

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