MHC class I- and class II-restricted processing and presentation of microencapsulated antigens

Men, Ying; Audran, R; Thomasin, Claudio; Eberl, Gérard; Demotz, Stéphane; Merkle, Hans P.; Gander, Bruno; Corradin, Giampietro

doi:10.1016/s0264-410x(98)00321-1

Cited by 116 publications

(63 citation statements)

References 56 publications

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“…One potential reason for the difference between protamine-coated and protamine-free particles with respect to their interaction with APCs could be differences in the particles size distribution of the formulations. In this study, the size distribution of the uncoated OVA-containing microparticles was ideal for uptake, since 90% of the particles were smaller than 6.4 μm, and only particles smaller than 5-10 μm have been shown to be efficiently taken up by antigen-presenting cells [7] and [33]. However, as the protaminecoated microparticles had a broader size distribution than the uncoated ones, with only 50% of the particles being smaller than 7.2 μm, the size cannot explain the differences in vitro and in vivo immune responses.…”

Section: Discussionmentioning

confidence: 99%

Surface coating of PLGA microparticles with protamine enhances their immunological performance through facilitated phagocytosis

Gómez

Csaba

Fischer

et al. 2008

Journal of Controlled Release

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Surface modifications of poly(lactide-co-glycolide) microparticles with different polycationic electrolytes have mainly been studied for conjugation to antigens and/or adjuvants. However, the in vivo immunological effects of using surface charged particles have not been address yet. In this study, microparticles were coated or not with protamine, a cationic and arginine-rich electrolyte that confers microparticles with a positively surface charge. We then evaluated the potential of protamine-coatings to assist the induction of immune responses in mice. Interestingly, enhanced antibodies and T-cell responses were observed in mice treated with the coated particles. In vitro studies suggested that the improved immunological performance was mediated by an increased uptake. Indeed, protamine-coated particles that carried a plasmid were even internalised into non-phagocytic cells and to cause their transfection. These results open the way for further research into a novel technology that combines the use protamine for facilitated cell penetration of that and biodegradable microparticles for prolonged antigen or drug release.

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Section: Discussionmentioning

confidence: 99%

Surface coating of PLGA microparticles with protamine enhances their immunological performance through facilitated phagocytosis

Gómez

Csaba

Fischer

et al. 2008

Journal of Controlled Release

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“…Microparticles are valuable carriers for the targeting of antigens to APC because they have been demonstrated to be efficiently phagocytosed by DC in vitro (3,13) and in vivo (14). In addition, phagocytosed microparticles release encapsulated antigen into the cells where it is efficiently presented on major histocompatibility complex (MHC) I and MHC II (15). Moreover, phagocytosed PLGA and PLA microparticles have been found to activate monocytes in vitro (16).…”

Section: Introductionmentioning

confidence: 99%

Composition and Surface Charge of DNA-Loaded Microparticles Determine Maturation and Cytokine Secretion in Human Dendritic Cells

Jilek¹,

Ulrich²,

Merkle³

et al. 2004

Pharm Res

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Purpose. Biodegradable microparticles prepared from poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) have been shown to be promising carrier systems for vaccine delivery. Here, we have investigated the capacity of different PLA and PLGA microparticle formulations to induce stimulation of human blood monocyte-derived dendritic cells (DCs). Methods. Stimulation of human derived dendritic cells by plain microparticles were compared with microparticles loaded with plasmid DNA or double-stranded salmon DNA either by encapsulation or adsorption to the surface of cationic microparticles. Stimulation of DCs was monitored by the up-regulation of surface maturation markers CD83 and CD86 and the secretion of IL-12 and TNF-␣. Results. Slowly degrading PLA microparticles did not induce any detectable stimulation or activation of DCs. In contrast, fast degrading PLGA microparticles were able to influence DC maturation and cytokine secretion dependent on their surface charge. Anionic PLGA microparticles induced an up-regulation of CD83 and high TNF-␣ secretion, which was further enhanced up to the level of the potent stimulator lipopolysaccharide (LPS) when plasmid DNA was encapsulated. Moreover, the secretion of significant amounts of IL-12 was observed. Cationic PLGA microparticles induced an up-regulation of CD86 and moderate TNF-␣ secretion, but no IL-12 secretion, with no additional effects in the presence of plasmid DNA. Conclusions. The data suggest that the composition and charge of biodegradable DNA-loaded microparticles profoundly influences maturation and cytokine secretion in DCs. Thus, the individual formulation of microparticles used as a vaccine carrier system might considerably influence the profile of the immune response.

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“…Earlier significant studies have shown that potent cell-mediated immunity induced by PLG microparticles following vaccination is likely to be due to the uptake of PLG microparticles into APCs and the effective delivery of microparticle-containing APCs to specific lymphoid compartments [25,32,33]. The size of PLG microparticles used for animal vaccination is a crucial parameter in facilitating the uptake of APCs [32].…”

Section: Microparticles-immune System Interactionmentioning

confidence: 99%

“…Following the uptake of microparticles, the APCs containing microparticles then migrate to other lymphoid compartments [25], such as the spleen and mesenteric lymph nodes, where they effectively present antigenic epitopes to T lymphocytes, especially Th1 and Tc, thereby inducing strong specific cell-mediated immunity [32,33]. In other words, facilitation of uptake and delivery of PLG microparticles by APCs can lead to more effective antigen processing and presentation to T lymphocytes capable of inducting cell-mediated immune responses [25,[32][33][34]. Significant earlier studies have further demonstrated that the APCs containing microparticles can travel to specialized mucosal lymphoid compartments, including mucosal-associated lymphoid tissues (MALTs), the inductive sites for stimulating potent immunity following intranasal or oral vaccination [35,36].…”

Section: Microparticles-immune System Interactionmentioning

confidence: 99%

Microparticle Vaccines Against Toxoplasma gondii

Yang¹

2017

Toxoplasmosis

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Significant information indicates that future investigations on Toxoplasma vaccine development have to include adjuvants for enhancing protective immunity against Toxoplasma gondii. Especially, safe and effective adjuvants capable of fulfilling Th1-dependent cellmediated immunity appear to be more likely to be allowed to use for anti Toxoplasma vaccine development. Recently, biodegradable and biocompatible polymers, such as poly (lactide-co-glycolide) (PLG) polymers, have been utilized as safe and efficacious adjuvants to encapsulate antigens for producing long-term release microparticle-based vaccines. PLG microencapsulation allows the sustained release of antigens and facilitates antigen uptake via antigen-presenting cells (APCs) to favorably generate Th1 cell-mediated immunity, which is required for the prevention of T. gondii infection. In our recent work, recombinant surface antigens (rSAGs), including rSAG1, rSAG2, and rSAG1/2, have been, respectively, encapsulated with the PLG polymer for production of PLG-encapsulated rSAG1 (PLG-rSAG1), PLG-encapsulated rSAG2 (PLG-rSAG2), or PLG-encapsulated rSAG1/2 (PLG-rSAG1/2) microparticles. This chapter describes adjuvant effect of PLG microparticles, controlled release of PLG microparticles, PLG microparticles-immune system interaction, Toxoplasma SAG-loaded PLG microparticles, protective immunity by Toxoplasma SAG-loaded PLG microparticles, and future prospects. PLG microparticle vaccines would be advantageous for their application in the development of long-lasting vaccines against T. gondii for future use in humans and animals.

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MHC class I- and class II-restricted processing and presentation of microencapsulated antigens

Cited by 116 publications

References 56 publications

Surface coating of PLGA microparticles with protamine enhances their immunological performance through facilitated phagocytosis

Surface coating of PLGA microparticles with protamine enhances their immunological performance through facilitated phagocytosis

Composition and Surface Charge of DNA-Loaded Microparticles Determine Maturation and Cytokine Secretion in Human Dendritic Cells

Microparticle Vaccines Against Toxoplasma gondii

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