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Ka-Yee Au, Wei-Wei Shi, Shuai Qian, Zhong Zuo, Pang-Chui Shaw
To improve the pharmacological properties of maize ribosome-inactivating protein (maize RIP) for targeting HIV-infected cells, the previously engineered TAT-fused active form of maize RIP (MOD) was further engineered for cysteine-directed PEGylation. In this work, two potential antigenic sites, namely Lys-78 and Lys-264, were identified. They were mutated to cysteine residue and conjugated with PEG5k or PEG20k. The resultant PEG derivatives of MOD variants were examined for ribosome-inactivating activity, circulating half-life and immunogenicity...
October 17, 2016: Toxins
Takeshi Kimura, Akihiro Yamashita, Keiichi Ozono, Noriyuki Tsumaki
Articular cartilage damage does not spontaneously heal and could ultimately result in a loss of joint function. Damaged cartilage can be repaired with cell/tissue sources that are transplanted, however, autologous chondrocytes are limited in number as a cell source. Induced pluripotent stem cells (iPSCs) are a relatively new and abundant cell source and can be made from the patient, but at considerable cost. Because cartilage is immunoprivileged tissue, allogeneic cartilages have been transplanted effectively without matching for human leukocyte antigen (HLA), but are difficult to acquire due to scarcity of donors...
October 20, 2016: Tissue Engineering. Part A
G MuŽíková, R Laga
Vaccines have helped considerably in eliminating some life-threatening infectious diseases in past two hundred years. Recently, human medicine has focused on vaccination against some of the world's most common infectious diseases (AIDS, malaria, tuberculosis, etc.), and vaccination is also gaining popularity in the treatment of cancer or autoimmune diseases. The major limitation of current vaccines lies in their poor ability to generate a sufficient level of protective antibodies and T cell responses against diseases such as HIV, malaria, tuberculosis and cancers...
October 20, 2016: Physiological Research
Canna Ghia, Shashank Akerkar, Shailaja Sabnis, Urk Rao, Gautam Rambhad
BACKGROUND / OBJECTIVES: Biologic anti-TNFs in India have improved the patient management. Significant proportions of patients lose response over time or do not respond. Possible explanations are suboptimal trough anti-TNFa concentrations or antibodies to anti-TNFs. The aim of this project was to set up and standardize an independent laboratory to test immunogenicity of anti-TNF biologics (infliximab and etanercept). METHODS: Three rheumatologists piloted this project approved by independent ethics committee and carried out in compliance with ICH/GCP guidelines...
September 2016: Journal of the Association of Physicians of India
Çiğdem Yılmaz, Aycan Apak, Erkan Özcengiz, Gülay Özcengiz
Whooping cough (pertussis) is a highly contagious respiratory infection caused by Bordetella pertussis. Although availability of effective pertussis vaccines seems to decrease the incidence of the disease, B. pertussis circulation in population has not been eliminated. Thus, finding new protein candidates with high immune protective capacities is necessary to enhance the efficacy of current acellular pertussis (Pa) vaccines. In this study, iron superoxide dismutase (FeSOD) gene (sodB) was cloned, expressed in Escherichia coli and recombinant FeSOD protein was purified...
October 20, 2016: Microbiology and Immunology
Navnit Kumar Mishra, Anil Kumar Sharma, Tapan Kumar Mukherjee
Melanoma is a cancer associated with melanocytes of epidermis. There has been a consistent increase in the number of melanoma patients because of the depletion of the ozone layer which makes it of paramount importance to explore the immunogenic potential of various peptides in melanoma therapy. In the current study, a mutated decapeptide (ELAGIGILTV) epitope ID 12941 was taken from the melanoma antigen recognized by T-cells. This epitope displayed relatively better affinity for histocompatibility leukocyte antigen influencing the proliferation of cytotoxic T-cells...
November 2016: Journal of Molecular Modeling
Kunihiko Watanabe
It is becoming well-known that bacterial cells produce membrane vesicles (MVs) from the cell surface in a budding manner, whereas the detailed mechanisms of MV biogenesis remain unclear. MVs are not authentic cells, since they are observed to be between 20 and 300 nm in size but have a structure close to the subcellular compartments. In a sense, the structure of MVs containing biogenic and cellular substances and their behavior look similar to those of viruses. Due to these scientific facts, several potent applications employing MVs as a promising tool have been proposed and reported...
October 19, 2016: Applied Microbiology and Biotechnology
Corinna La Rosa, Jeff Longmate, Joy Martinez, Qiao Zhou, Teodora I Kaltcheva, Weimin Tsai, Jennifer Drake, Mary Carroll, Felix Wussow, Flavia Chiuppesi, Nicola Hardwick, Sanjeet Dadwal, Ibrahim Aldoss, Ryotaro Nakamura, John A Zaia, Don J Diamond
Attenuated poxvirus Modified vaccinia Ankara (MVA) is a useful viral-based vaccine for clinical investigation, because of its excellent safety profile and property of inducing potent immune responses against recombinant (r) antigens. We developed Triplex by constructing an rMVA encoding three immunodominant CMV antigens which stimulates a host anti-viral response: UL83 (pp65), UL123 (IE1-exon4), and UL122 (IE2-exon5). We completed the first clinical evaluation of the Triplex vaccine in 24 healthy adults, with or without immunity to CMV and vaccinia virus (previous DryVax smallpox vaccination)...
October 19, 2016: Blood
Yann Desfougères, Jean-Michel Poitou, Henri Wróblewski, Laure Béven
Spiralin is the most abundant protein of several species of spiroplasmas, helical, motile bacteria pathogenic for arthropods and plants. This amphiphilic protein is anchored to the outer face of the plasma membrane by a lipoylated N-terminal cysteine. Although spiroplasma pathogenicity in mammals is controversial, it was shown that spiralin is highly immunogenic and endowed with immunomodulatory activity. In this paper, we describe a high performance method for the purification of Spiroplasma melliferum spiralin under non-denaturing conditions...
October 12, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Katarzyna A Radomska, Mahdi M Vaezirad, Koen M Verstappen, Marc M S M Wösten, Jaap A Wagenaar, Jos P M van Putten
Campylobacter jejuni is the main cause of bacterial food-borne diseases in developed countries. Chickens are the most important source of human infection. Vaccination of poultry is an attractive strategy to reduce the number of C. jejuni in the intestinal tract of chickens. We investigated the immunogenicity and protective efficacy of a recombinant C. jejuni flagellin-based subunit vaccine with intrinsic adjuvant activity. Toll-like receptor activation assays demonstrated the purity and TLR5 stimulating (adjuvant) activity of the vaccine...
2016: PloS One
Myriam Arévalo-Herrera, Juan M Vásquez-Jiménez, Mary Lopez-Perez, Andrés F Vallejo, Andrés B Amado-Garavito, Nora Céspedes, Angélica Castellanos, Karen Molina, Johanna Trejos, José Oñate, Judith E Epstein, Thomas L Richie, Sócrates Herrera
BACKGROUND: Immunizing human volunteers by mosquito bite with radiation-attenuated Plasmodium falciparum sporozoites (RAS) results in high-level protection against infection. Only two volunteers have been similarly immunized with P. vivax (Pv) RAS, and both were protected. A phase 2 controlled clinical trial was conducted to assess the safety and protective efficacy of PvRAS immunization. METHODOLOGY/PRINCIPAL FINDINGS: A randomized, single-blinded trial was conducted...
October 2016: PLoS Neglected Tropical Diseases
Y Wang, J Guo, S Qiao, Q Li, J Yang, Q Jin, G Zhang
Porcine reproductive and respiratory syndrome virus (PRRSV) is an important swine pathogen, causing huge economic losses each year worldwide. Immunization with vaccines containing the glycoprotein 5 (GP5) of PRRSV is the main measure to induce neutralizing antibodies and control the disease. Here, we developed a GP5 protein-based ELISA for detecting antibodies against PRRSV. The overall yield of purified GP5 in E. coli flask culture was more than 45 mg/L cell culture. Western blot and IFA indicated that the GP5 protein was highly immunogenic...
September 1, 2016: Polish Journal of Veterinary Sciences
Behjatolah Monzavi-Karbassi, Fariba Jousheghany, Thomas Kieber-Emmons
Development of cancer vaccines targeting tumor-associated antigens (TAAs) is an alternative approach to chemotherapy with sustained anti-tumor effects. The success of active immunotherapy has been hampered by tumor-induced immune suppressors. Regulatory T cells (Tregs) are a population of immune suppressors with a proven role in regulating anti-tumor immune responses. Removing or subduing Tregs activity leads to more robust anti-tumor immune responses. Here, we used a cell-based vaccination strategy in the 4T1 murine mammary model to examine whether bulk removal of certain TAAs, using their glycan profile, can affect the immunogenicity of the vaccine...
October 19, 2016: Immunological Investigations
Bagirath Gangadharan, Mathieu Ing, Sandrine Delignat, Ivan Peyron, Maud Teyssandier, Srinivas V Kaveri, Sébastien Lacroix-Desmazes
The development of inhibitory antibodies to therapeutic FVIII is the major complication of replacement therapy in patients with hemophilia A. The first step in the initiation of the anti-FVIII immune response is FVIII interaction with receptor(s) on antigen-presenting cells followed by endocytosis and presentation to naive CD4+ T cells. Recent studies indicate a role for the C1 domain in FVIII uptake. We investigated whether charged residues in the C2 domain participate in immunogenic FVIII uptake. Co-incubation of FVIII with BO2C11, a monoclonal C2-specific IgG, reduced FVIII endocytosis by dendritic cells and presentation to CD4+ T cells, and diminished FVIII immunogenicity in FVIII-deficient mice...
October 6, 2016: Haematologica
Laura Martelli, Laurent Peyrin-Biroulet
BACKGROUND: Anti-tumor necrosis factor (anti-TNF) monoclonal antibodies have revolutionized the treatment of inflammatory bowel diseases (IBD). However, because of their complexity, their production is expensive contributing to their high price. As the patent protection of these therapies has expired in several countries, biosimilars have been developed to reduce the healthcare costs. The aim of this article is to review the literature on the safety, efficacy and immunogenicity of biosimilars in IBD...
October 14, 2016: Current Medicinal Chemistry
Zhizhen Chen, Liping Wang, Tianshu Xu, Qifei Wang, Lishan Kang, Qi Zhao
Bispecific antibodies with binding specificities for two different antigens have prompted a lot of interest into their development and application. Currently, more than ten bispecific antibodies have been clinically validated for the treatment of various diseases, including cancers and inflammatory diseases. Intensive studies in antibody engineering drive the generation of different bispecific antibody formats that differ in size and shape. However, the most prominent formats, such as IgG-single-chain (sc) Fv or dual-variable domain (DVD) IgG, deviating from the natural IgG structure, may lead to manufacturing difficulties or increase the potential risk of immunogenicity...
October 18, 2016: Current Pharmaceutical Biotechnology
Abbas Shahsavari, Mehdi Azad, Naser Mobarra, Koorosh Goodarzvand Chegini, Nematollah Gheibi
Calprotectin is member of the S-100 protein family with a wide plethora of intra-and extracellular functions. Anticancer activities, antimicrobial effects and being a qualified disease marker are among the compelling features of this protein to be used as a pharmaceutical agent. However, there are several impediments to applications of protein pharmaceuticals including: proteolytic degradation, short circulating half-life, low solubility and immunogenicity. Pegylation is a common bioconjugation polymer capable of overcoming these drawbacks...
October 18, 2016: Protein Journal
Wataru Obara, Takashi Karashima, Kazuyoshi Takeda, Renpei Kato, Yoichiro Kato, Mitsugu Kanehira, Ryo Takata, Keiji Inoue, Toyomasa Katagiri, Taro Shuin, Yusuke Nakamura, Tomoaki Fujioka
PURPOSE: Through genome-wide expression profile analysis, hypoxia-inducible protein 2 (HIG2) has previously been identified as an oncoprotein involved in development/progression of renal cell carcinoma (RCC). We subsequently identified a highly immunogenic HLA-A*0201/0206-restricted epitope peptide (HIG2-9-4) corresponding to a part of HIG2 and applied it as a therapeutic vaccine. We conducted a phase I clinical trial using the HIG2-9-4 peptide for patients with advanced RCC. MATERIALS AND METHODS: Nine patients having HLA-A*0201 or HLA-A*0206 with metastatic or unresectable RCC after failure of the cytokine and/or tyrosine kinase inhibitor therapies were enrolled in this study...
October 18, 2016: Cancer Immunology, Immunotherapy: CII
Andrew Zloza, Neal D Dharmadhikari, Erica J Huelsmann, Joseph R Broucek, Tasha Hughes, Frederick J Kohlhapp, Howard L Kaufman
Recombinant interleukin-2 (rIL-2) is associated with objective responses in 15-20 % of patients with metastatic melanoma and renal cell carcinoma. More recently, rIL-2 has also demonstrated improved clinical activity in patients with melanoma. Given the toxicity of high-dose rIL-2 and the availability of many new immunotherapy agents, it has been suggested that lower doses of rIL-2 may be preferred for combination clinical studies. In order to determine the impact of low doses of rIL-2 on anti-tumor immunity and therapeutic effectiveness, we challenged C57BL/6 mice with poorly immunogenic B16-F10 melanoma and treated them with varying doses of rIL-2 (range 10(3)-10(5) IU)...
October 18, 2016: Cancer Immunology, Immunotherapy: CII
Erika Vacchelli, Norma Bloy, Fernando Aranda, Aitziber Buqué, Isabelle Cremer, Sandra Demaria, Alexander Eggermont, Silvia Chiara Formenti, Wolf Hervé Fridman, Jitka Fucikova, Jérôme Galon, Radek Spisek, Eric Tartour, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
Malignant cells succumbing to some forms of radiation therapy are particularly immunogenic and hence can initiate a therapeutically relevant adaptive immune response. This reflects the intrinsic antigenicity of malignant cells (which often synthesize a high number of potentially reactive neo-antigens) coupled with the ability of radiation therapy to boost the adjuvanticity of cell death as it stimulates the release of endogenous adjuvants from dying cells. Thus, radiation therapy has been intensively investigated for its capacity to improve the therapeutic profile of several anticancer immunotherapies, including (but not limited to) checkpoint blockers, anticancer vaccines, oncolytic viruses, Toll-like receptor (TLR) agonists, cytokines, and several small molecules with immunostimulatory effects...
2016: Oncoimmunology
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