Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mounting of a specific immune response against the human papillomavirus type 16 E7 protein (HPV16 E7) is important for eradication of HPV16 E7-expressing cancer cells from the cervical mucosa. To induce a mucosal immune response by oral delivery of the E7 antigen, we expressed the HPV16 E7 antigen on the surface of Lactobacillus casei by employing a novel display system in which the poly-gamma-glutamic acid (gamma-PGA) synthetase complex A (PgsA) from Bacillus subtilis (chungkookjang) was used as an anchoring motif. After surface expression of the HPV16 E7 protein was confirmed by Western blot, flow cytometry and immunofluorescence microscopy, mice were orally inoculated with L. casei-PgsA-E7. E7-specific serum IgG and mucosal IgA productions were enhanced after oral administration and significantly enhanced after boosting. Systemic and local cellular immunities were significantly increased after boosting, as shown by increased counts of lymphocytes (SI = 9.7 +/- 1.8) and IFN-gamma secreting cells [510 +/- 86 spot-forming cells/10(6)cells] among splenocytes and increased IFN-gamma in supernatants of vaginal lymphocytes. Furthermore, in an E7-based mouse tumor model, animals receiving orally administered L. casei-PgsA-E7 showed reduced tumor size and increased survival rate versus mice receiving control (L. casei-PgsA) immunization. These results collectively indicate that the oral administration of E7 displayed on lactobacillus induces cellular immunity and antitumor effects in mice.
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PMID:Oral administration of human papillomavirus type 16 E7 displayed on Lactobacillus casei induces E7-specific antitumor effects in C57/BL6 mice. 1664 80

Nanoparticles are considered to be efficient tools for inducing potent immune responses by an Ag carrier. In this study, we examined the effect of Ag-carrying biodegradable poly(gamma-glutamic acid) (gamma-PGA) nanoparticles (NPs) on the induction of immune responses in mice. The NPs were efficiently taken up by dendritic cells (DCs) and subsequently localized in the lysosomal compartments. gamma-PGA NPs strongly induced cytokine production, up-regulation of costimulatory molecules, and the enhancement of T cell stimulatory capacity in DCs. These maturational changes of DCs involved the MyD88-mediated NF-kappaB signaling pathway. In vivo, gamma-PGA NPs were preferentially internalized by APCs (DCs and macrophages) and induced the production of IL-12p40 and IL-6. The immunization of mice with OVA-carrying NPs induced Ag-specific CTL activity and Ag-specific production of IFN-gamma in splenocytes as well as potent production of Ag-specific IgG1 and IgG2a Abs in serum. Furthermore, immunization with NPs carrying a CD8(+) T cell epitope peptide of Listeria monocytogenes significantly protected the infected mice from death. These results suggest that Ag-carrying gamma-PGA NPs are capable of inducing strong cellular and humoral immune responses and might be potentially useful as effective vaccine adjuvants for the therapy of infectious diseases.
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PMID:Targeting of antigen to dendritic cells with poly(gamma-glutamic acid) nanoparticles induces antigen-specific humoral and cellular immunity. 1731 43

We analyzed the in vivo tumor regression activity of high molecular mass poly-gamma-glutamate (gamma-PGA) from Bacillus subtilis sups. chungkookjang. C57BL/6 mice were orally administered 10-, 100-, or 2000-kDa gamma-PGA or beta-glucan (positive control), and antitumor immunity was examined. Our results revealed higher levels of NK cell-mediated cytotoxicity and IFN-gamma secretion in mice treated with higher molecular mass gamma-PGA (2000 kDa) vs those treated with lower molecular mass gamma-PGA (10 or 100 kDa) or beta-glucan. We then examined the effect of oral administration of 10- or 2000-kDa gamma-PGA on protection against B16 tumor challenge in C57BL/6 mice. Mice receiving high molecular mass gamma-PGA (2000 kDa) showed significantly smaller tumor sizes following challenge with the MHC class I-down-regulated tumor cell lines, B16 and TC-1 P3 (A15), but not with TC-1 cells, which have normal MHC class I expression. Lastly, we found that gamma-PGA-induced antitumor effect was decreased by in vivo depletion of NK cells using mAb PK136 or anti-asialo GM1 Ab, and that was completely blocked in NK cell-deficient B6 beige mice or IFN-gamma knockout mice. Taken together, we demonstrated that oral administration of high molecular mass gamma-PGA (2000 kDa) generated significant NK cell-mediated antitumor activity in mice bearing MHC class I-deficient tumors.
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PMID:Oral administration of high molecular mass poly-gamma-glutamate induces NK cell-mediated antitumor immunity. 1761 66

Antigen delivery systems using polymeric nanoparticles are of special interest as stable protein-based antigen carriers. In the present study, novel biodegradable poly(gamma-glutamic acid) (gamma-PGA) nanoparticles were examined for their antigen delivery and immunostimulatory activities in vitro and in vivo. The uptake of ovalbumin by dendritic cells was markedly enhanced by gamma-PGA nanoparticles, and the ovalbumin was gradually released from gamma-PGA nanoparticles into the cells. In addition, gamma-PGA nanoparticles appeared to have great potential as an adjuvant, because they could induce the maturation of dendritic cells. Although not only ovalbumin-encapsulating nanoparticles (OVA-NPs) but also a simple mixture of ovalbumin and nanoparticles induced dendritic cell maturation, the only dendritic cells exposed to OVA-NPs could strongly activate antigen-specific interferon (IFN)-gamma-producing T cells. Subcutaneous immunization of mice with human immunodeficiency virus type 1 (HIV-1) p24-encapsulating nanoparticles activated antigen-specific IFN-gamma-producing T cells in spleen cells and induced p24-specific serum antibodies, as compared to immunization with p24 alone. Like ovalbumin, a mixture of p24 and nanoparticles also induced antigen-specific serum antibodies but did not activate IFN-gamma-producing T cells in spleen cells, suggesting that nanoparticles play a critical role in inducing cellular immune responses. Furthermore, gamma-PGA nanoparticles had a capacity comparable to that of the complete Freund's adjuvant (CFA) in inducing p24-specific serum antibody. However, unlike CFA, they predominantly activated p24-specific IFN-gamma-producing T cells. Thus, gamma-PGA nanoparticles encapsulating various antigens may have great potential as novel and efficient protein-based vaccines against infectious diseases, including HIV-1 infection.
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PMID:Poly(gamma-glutamic acid) nanoparticles as an efficient antigen delivery and adjuvant system: potential for an AIDS vaccine. 1804 Oct 33