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Si Houn Hahn, David Kronn, Nancy D Leslie, Loren D M Pena, Pranoot Tanpaiboon, Michael J Gambello, James B Gibson, Richard Hillman, David W Stockton, John W Day, Raymond Y Wang, Kristina An Haack, Raheel Shafi, Susan Sparks, Yang Zhao, Catherine Wilson, Priya S Kishnani
PurposePompe disease results from lysosomal acid α-glucosidase (GAA) deficiency and its associated glycogen accumulation and muscle damage. Alglucosidase alfa (recombinant human GAA (rhGAA)) received approval in 2006 as a treatment for Pompe disease at the 160 L production scale. In 2010, larger-scale rhGAA was approved for patients up to 8 years old without cardiomyopathy. NCT01526785 evaluated 4,000 L rhGAA efficacy/safety in US infantile- or late-onset Pompe disease (IOPD, LOPD) patients up to 1 year old transitioned from 160 L rhGAA...
March 22, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
Peng-Jie Yang, Wei-Xin Yuan, Jia Liu, Jin-Ying Li, Bing Tan, Chen Qiu, Xiao-Long Zhu, Cong Qiu, Dong-Mei Lai, Li-He Guo, Lu-Yang Yu
Human amniotic epithelial cells (hAECs), derived from the innermost layer of the term placenta closest to the fetus, have been shown to be potential seed cells for allogeneic cell therapy. Previous studies have shown a certain therapeutic effect of hAECs. However, no appropriate isolation and culture system for hAECs has been developed for clinical applications. In the present study, we established a serum-free protocol for hAEC isolation and cultivation, in which better cell growth was observed compared with that in a traditional culture system with serum...
March 22, 2018: Acta Pharmacologica Sinica
Elena Garreta, Sonia Sanchez, Jeronimo Lajara, Nuria Montserrat, Juan Carlos Izpisua Belmonte
Purpose of Review: The goal of this paper is to highlight the major challenges in the translation of human pluripotent stem cells into a clinical setting. Recent Findings: Innate features from human induced pluripotent stem cells (hiPSCs) positioned these patient-specific cells as an unprecedented cell source for regenerative medicine applications. Immunogenicity of differentiated iPSCs requires more research towards the definition of common criteria for the evaluation of innate and host immune responses as well as in the generation of standardized protocols for iPSC generation and differentiation...
2018: Current Transplantation Reports
Blaise Corthésy, Gilles Bioley
Vaccination is the process of administering immunogenic formulations in order to induce or harness antigen (Ag)-specific antibody and T cell responses in order to protect against infections. Important successes have been obtained in protecting individuals against many deleterious pathological situations after parenteral vaccination. However, one of the major limitations of the current vaccination strategies is the administration route that may not be optimal for the induction of immunity at the site of pathogen entry, i...
2018: Frontiers in Immunology
Sadhana Mangwana, Vivek Gangwar
The Kell blood group system is complex, contains many antigens, highly immunogenic, and potent in triggering immune reactions. Antibodies to Kell blood group system are the most common immune red cell antibodies, following ABO and Rh. However, among the anti-Kell antibodies; anti-Kpa is extremely rare. We report an interesting case of Anti-Kpa in a 59-year-old female patient of Non-Hodgkin's Lymphoma, post radiotherapy, who first developed warm autoantibody and later developed anti-Kpa alloantibody on multiple transfusions...
January 2018: Asian Journal of Transfusion Science
M Justin Iampietro, Rafael A Larocca, Nicholas M Provine, Peter Abbink, Zi Han Kang, Christine A Bricault, Dan H Barouch
Adenovirus (Ad) vectors are being investigated as vaccine candidates, but baseline anti-vector immunity exists in human populations to both human Ad (HuAd) and chimpanzee Ad (ChAd) vectors. In this study, we investigated the immunogenicity and cross-reactivity of a panel of recently described rhesus adenoviral (RhAd) vectors. RhAd vectors elicited T cells with low exhaustion markers and robust anamnestic potential. Moreover, RhAd vector immunogenicity was unaffected by high levels of pre-existing anti-HuAd immunity...
March 21, 2018: Journal of Virology
I K Ragan, A S Davis, D S McVey, J A Richt, R R Rowland, W C Wilson
Rift Valley Fever virus (RVFV) is a mosquito-borne zoonotic virus that infects ruminants including cattle, sheep, goats, camels and buffalo. Multiplexing diagnostic assays that can simultaneously detect antibodies against multiple RVFV antigens offer a high throughput test for disease surveillance and vaccine evaluations. We describe the improvement and evaluation of a previously developed fluorescence microsphere immunoassay (FMIA) for the detection of IgG and IgM antibodies against the RVFV glycoproteins (Gn) and the immunogenic nucleocapsid protein (Np)...
March 21, 2018: Journal of Clinical Microbiology
Steffen Dettling, Slava Stamova, Rolf Warta, Martina Schnölzer, Carmen Rapp, Anchana Rathinasamy, David Reuss, Kolja Pocha, Saskia Roesch, Christine Jungk, Uwe Warnken, Volker Eckstein, Niels Grabe, Christoph Schramm, Markus A Weigand, Andreas von Deimling, Andreas Unterberg, Philipp Beckhove, Christel Herold-Mende
PURPOSE: Successful immunotherapies for IDH mut gliomas require better knowledge of T-cell target antigens. Here, we elucidated their antigen repertoire recognized by spontaneous T-cell responses using an unbiased proteomic approach. EXPERIMENTAL DESIGN: Protein fractionations of tissue lysates from IDH mut gliomas (n=4) were performed. Fractions were tested by IFN-ᵯE; ELISpot assay for recognition through patient's T-cells. Proteins of immunogenic fractions were identified by mass spectrometry and validated by in silico-predicted synthetic long-peptides in patients of origin, additional IDH mut glioma patients (n=16), and healthy donors (n=13)...
March 21, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Marta Magatti, Elsa Vertua, Anna Cargnoni, Antonietta Silini, Ornella Parolini
Among the many cell types useful in developing therapeutic treatments, human amniotic cells from placenta have been proposed as valid candidates. Both human amniotic epithelial and mesenchymal stromal cells, and the conditioned medium generated from their culture, exert multiple immunosuppressive activities. Indeed, they inhibit T and B cell proliferation, suppress inflammatory properties of monocytes, macrophages, dendritic cells, neutrophils, and natural killer cells, while promoting induction of cells with regulatory functions such as regulatory T cells and anti-inflammatory M2 macrophages...
January 2018: Cell Transplantation
B Barboni, V Russo, P Berardinelli, A Mauro, L Valbonetti, H Sanyal, A Canciello, L Greco, A Muttini, V Gatta, L Stuppia, M Mattioli
The field of regenerative medicine is moving toward clinical practice in veterinary science. In this context, placenta-derived stem cells isolated from domestic animals have covered a dual role, acting both as therapies for patients and as a valuable cell source for translational models. The biological properties of placenta-derived cells, comparable among mammals, make them attractive candidates for therapeutic approaches. In particular, stemness features, low immunogenicity, immunomodulatory activity, multilineage plasticity, and their successful capacity for long-term engraftment in different host tissues after autotransplantation, allo-transplantation, or xenotransplantation have been demonstrated...
January 2018: Cell Transplantation
Taja Železnik Ramuta, Mateja Erdani Kreft
Human amniotic membrane (hAM) is the innermost layer of fetal membranes, which surrounds the developing fetus and forms the amniotic cavity. hAM and hAM-derived cells possess many properties that make them suitable for use in regenerative medicine, such as low immunogenicity, promotion of epithelization, anti-inflammatory properties, angiogenic and antiangiogenic properties, antifibrotic properties, antimicrobial properties, and anticancer properties. Many pathological conditions of the urinary tract lead to organ damage or complete loss of function...
January 2018: Cell Transplantation
Marlena M Westcott, Jason Smedberg, Matthew J Jorgensen, Shelby Puckett, Douglas S Lyles
Recombinant vesicular stomatitis virus (VSV) is a promising platform for vaccine development. M51R VSV, an attenuated, M protein mutant strain, is an effective inducer of Type I interferon and dendritic cell (DC) maturation, which are desirable properties to exploit for vaccine design. We have previously evaluated M51R VSV (M51R) and M51R VSV that produces flagellin (M51R-F) as vaccine vectors using murine models, and found that flagellin enhanced DC activation and VSV-specific antibody production after low-dose vaccination...
March 19, 2018: Vaccines
Yoshihiro Morita, Macall Leslie, Hiroyasu Kameyama, David E Volk, Takemi Tanaka
Aptamer-related technologies represent a revolutionary advancement in the capacity to rapidly develop new classes of targeting ligands. Structurally distinct RNA and DNA oligonucleotides, aptamers mimic small, protein-binding molecules and exhibit high binding affinity and selectivity. Although their molecular weight is relatively small-approximately one-tenth that of monoclonal antibodies-their complex tertiary folded structures create sufficient recognition surface area for tight interaction with target molecules...
March 19, 2018: Cancers
Shufang He, Weiwei Fan, Na Wu, Jingjing Zhu, Yunqiu Miao, Xiaran Miao, Feifei Li, Xinxin Zhang, Yong Gan
RNA interference (RNAi) technology has shown great promise for the treatment of cancer and other genetic disorders. Despite the efforts to increase the target tissue distribution, the safe and effective delivery of siRNA to the diseased cells with sufficient cytosolic transport is another critical factor for successful RNAi clinical application. Here, the constructed lipid-based liquid crystalline nanoparticles, called nano-Transformers, can transform the structure in the intracellular acidic environment, and perform high-efficient siRNA delivery for cancer treatment...
March 21, 2018: Nano Letters
Huifeng Yu, Yanming An, Marcos Daniel Battistel, John F Cipollo, Darón I Freedberg
Conjugate vaccines are highly heterogeneous in terms of glycosylation sites and linked oligosaccharide length. Therefore, the characterization of conjugate vaccines' glycosylation state is challenging. However, improved product characterization can lead to enhancements in product control and product quality. Here, we present a synergistic combination of high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy for the analysis of glycoconjugates. We use the power of this strategy to characterize model polysaccharide conjugates to demonstrate a detailed level of glycoproteomic analysis...
March 21, 2018: Analytical Chemistry
Kei Nakashima, Masahiro Aoshima, Satoko Ohfuji, Satoshi Yamawaki, Masahiro Nemoto, Shinya Hasegawa, Satoshi Noma, Masafumi Misawa, Naoto Hosokawa, Makito Yaegashi, Yoshihito Otsuka
It is unclear whether simultaneous administration of a 23-valent pneumococcal polysaccharide vaccine (PPSV23) and a quadrivalent influenza vaccine (QIV) produces immunogenicity in older individuals. This study tested the hypothesis that the pneumococcal antibody response elicited by simultaneous administration of PPSV23 and QIV in older individuals is not inferior to that elicited by sequential administration of PPSV23 and QIV. We performed a single-center, randomized, open-label, non-inferiority trial comprising 162 adults aged ≥65 years randomly assigned to either the simultaneous (simultaneous injections of PPSV23 and QIV) or sequential (control; PPSV23 injected 2 weeks after QIV vaccination) groups...
March 21, 2018: Human Vaccines & Immunotherapeutics
Tomas Lorant, Mats Bengtsson, Torsten Eich, Britt-Marie Eriksson, Lena Winstedt, Sofia Järnum, Yvonne Stenberg, Anna-Karin Robertson, Kristina Mosén, Lars Björck, Lars Bäckman, Erik Larsson, Kathryn Wood, Gunnar Tufveson, Christian Kjellman
Safety, immunogenicity, pharmacokinetics and efficacy of the immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS, Imlifidase) was assessed in a single centre, open label ascending dose study in highly sensitised chronic kidney disease patients. Eight patients with cytotoxic panel-reactive antibodies (median cytotoxic PRA of 64%) at enrolment received 1 or 2 intravenous infusions of IdeS on consecutive days (0.12 mg/kg body weight x2 (n=3); 0.25 mg/kg x1 (n=3) or 0.25 mg/kg x2 (n=2)). IgG degradation was observed in all subjects after IdeS treatment, with <1% plasma IgG remaining within 48 hours and remaining low up to 7 days...
March 21, 2018: American Journal of Transplantation
Widodo, Nadya Veronica Margarecaesha Anyndita, Nurul Dluha, Muhaimin Rifa'i, Karimatul Himmah, Mulya Dwi Wahyuningsih
Background: Epstein-Barr virus (EBV) can cause cancer in people from around the world. There is no EBV vaccine available for use on a global scale. However, emerging evidence suggests that the epitope on the gp350/220 capsid protein may be developed into an EBV vaccine. Nevertheless, the production of small, single epitope is challenging of stability issues and possible alteration of peptide structure. In this study, a tandem epitope was developed consisting of three single epitopes, aimed to improve stability, antigenicity and preserve epitope structure...
March 2018: Heliyon
Hiroshi Uchi
Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with frequent metastasis and death. MCC has a mortality rate of 30%, making it more lethal than malignant melanoma, and incidence of MCC has increased almost fourfold over the past 20 years in the USA. MCC has long been considered to be an immunogenic cancer because it occurs more frequently in immunosuppressed patients from organ transplant and HIV infection than in those with immunocompetent. Chronic UV light exposure and clonal integration of Merkel cell polyomavirus (MCPyV) are two major causative factors of MCC...
2018: Frontiers in Oncology
Xiujuan Zhou, Jing Xing, Xiaoqian Tang, Wenbin Zhan
Outer membrane protein (Omp) K, OmpR and VAA have been identified with good immunogenicity from Vibrio anguillarum, and their recombinant proteins showed variable relative percent survival (RPS) in previous study. In order to develop effective bivalent vaccine candidates, recombinant (r) VAA + rOmpK (AK), rVAA + rOmpR (AR), rOmpK + rOmpR (KR) among VAA, OmpK and OmpR, or formalin-killed cells (FKC) of V. anguillarum were immunized in flounder, respectively. Results revealed that AK, AR, KR and FKC could induce the proliferation of surface membrane immunoglobulin-positive B lymphocytes or CD3+ T lymphocytes in peripheral blood lymphocytes, and significantly enhance the total antibodies, specific antibodies and immune-related gene than those of control group...
March 17, 2018: Developmental and Comparative Immunology
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