Synthetic peptides entrapped in microparticles can elicit cytotoxic T cell activity

Nixon, Douglas F.; Hioe, Catarina E.; Chen, Pei-de; Bian, Zuning; Kuebler, Peter; Li, Ming-Lie; Qiu, Howard; Li, Xuan‐Mao; Singh, Manmohan; Richardson, Julie; McGee, Paul; Zamb, Timothy J.; Koff, Wayne C.; Wang, Chang Yi; O’Hagan, Derek T.

doi:10.1016/s0264-410x(96)00099-0

Cited by 127 publications

(60 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They provided indirect evidence that ovalbumin encapsulated in the MPs was able to enter the cytoplasm of these cells and could activate the endoplasmic reticulum based MHC-1 pathway of antigen presentation to CD8+ T cells ('cross-presentation'). Many other groups had shown similar cross-presentation data from encapsulated protein antigens, or DNA in PLGA NPs or MPs (Audran et al, 2003;Nixon et al, 1996;Partidos et al, 1999). From such data it had been concluded by many that, rather than the antigen, it is the intact PLGA particles that lyse the phagosomal/endosomal membrane and subsequently release the antigen into the cytoplasm (Shen et al, 2006).…”

Section: Discussionmentioning

confidence: 90%

Polylactide-co-glycolide-rifampicin-nanoparticles efficiently clearMycobacterium bovisBCG infection in macrophages and remain membrane-bound in phago-lysosomes

Kalluru

Fenaroli

Westmoreland

et al. 2013

Journal of Cell Science

View full text Add to dashboard Cite

Summary Nanoparticles (NPs) are increasingly used as biodegradable vehicles to selectively deliver therapeutic agents such as drugs or antigens to cells. The most widely used vehicle for this purpose is based on copolymers of lactic acid and glycolic acid (PLGA) and has been extensively used in experiments aimed at delivering antibiotics against Mycobacterium tuberculosis in animal models of tuberculosis. Here, we describe fabrication of PLGA NPs containing either a high concentration of rifampicin or detectable levels of the green fluorescent dye, coumarin-6. Our goal here was twofold: first to resolve the controversial issue of whether, after phagocytic uptake, PLGA NPs remain membrane-bound or whether they escape into the cytoplasm, as has been widely claimed. Second, we sought to make NPs that enclosed sufficient rifampicin to efficiently clear macrophages of infection with Mycobacterium bovis BCG. Using fluorescence microscopy and immuno-electron microscopy, in combination with markers for lysosomes, we show that BCG bacteria, as expected, localized to early phagosomes, but that at least 90% of PLGA particles were targeted to, and remained in, low pH, hydrolaserich phago-lysosomes. Our data collectively argue that PLGA NPs remain membrane-enclosed in macrophages for at least 13 days and degrade slowly. Importantly, provided that the NPs are fabricated with sufficient antibiotic, one dose given after infection is sufficient to efficiently clear the BCG infection after 9-12 days of treatment, as shown by estimates of the number of bacterial colonies in vitro.

show abstract

Section: Discussionmentioning

confidence: 90%

Polylactide-co-glycolide-rifampicin-nanoparticles efficiently clearMycobacterium bovisBCG infection in macrophages and remain membrane-bound in phago-lysosomes

Kalluru

Fenaroli

Westmoreland

et al. 2013

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…This mechanism has been recognized for its role in immune responses against viruses, tumor immunity, and vaccine development. Till now, many kinds of particulate antigen delivery systems have been proved efficient to target exogenous antigen into the MHC-I pathway and to elicit CTL, such as immune-stimulating complexes (35), liposomes (2), virus-like particles (18), microspheres (22), and phage-displayed particles (8,38). It has been suggested that, compared with soluble antigens, particulate antigens are more easily captured by professional APCs such as DCs and macrophages and then become more efficiently transferred into the class I pathways (namely cross-presentation).…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

Section: Cd8mentioning

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

View full text Add to dashboard Cite

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...

show abstract

“…Particles bellow 2 μm migrated from the patches to mesenteric lymph nodes. Altered mucus layer during IBD, leaky epithelium and increased activity of the immunoregulatory cells in the inflamed mucosa are additional variables contributing to the improved localization of MPs and NPs at the site of inflammation but at the same time they assist the translocation and biological fate of the MP/NP-DDS to be even less predictable (Lamprecht, 2010;Nixon et al, 1996;Reece et al, 2001). Implementing previously stated targeting principles we have designed microparticulated polyelectrolyte muco/bioadhesive DDS for inflammation targeting using the enhanced permeability effect as targeting strategy Glavas Dodov et al, 2009;Simonoska Crcarevska et al, 2008).…”

Section: Physicochemical Properties Affecting the Efficacy Of The Ddsmentioning

confidence: 99%

Drug Targeting in IBD Treatment – Existing and New Approaches

Goračinova¹,

Dodov²,

Crcarevska³

et al. 2012

Inflammatory Bowel Disease - Advances in Pathogenesis and Management

View full text Add to dashboard Cite

Synthetic peptides entrapped in microparticles can elicit cytotoxic T cell activity

Cited by 127 publications

References 17 publications

Polylactide-co-glycolide-rifampicin-nanoparticles efficiently clearMycobacterium bovisBCG infection in macrophages and remain membrane-bound in phago-lysosomes

Polylactide-co-glycolide-rifampicin-nanoparticles efficiently clearMycobacterium bovisBCG infection in macrophages and remain membrane-bound in phago-lysosomes

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

Drug Targeting in IBD Treatment – Existing and New Approaches

Contact Info

Product

Resources

About