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immunogenicity TNF

Adey A Berhanu, Svetlana Krasnokutsky, Robert T Keenan, Michael H Pillinger
INTRODUCTION: Pegloticase is a highly effective therapy for patients with refractory and/or tophaceous gout, but has a high discontinuation rate (30-50%) due to development of anti-drug antibodies causing loss of efficacy and risk of infusion reactions. OBJECTIVE: To describe the use of azathioprine or other immunosuppressive therapies as a pegloticase adjunct to prevent pegloticase immunogenicity when treating gout. METHODS: Case report of azathioprine use in a patient receiving pegloticase therapy for refractory tophaceous gout, and review of the literature for the impact of immunosuppressive agents on development of anti-drug antibodies...
September 20, 2016: Seminars in Arthritis and Rheumatism
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
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
Himanshu Pandey, Sarita Tripathi, Kanchan Srivastava, Dinesh K Tripathi, Mrigank Srivastava, Surya Kant, Kishore K Srivastava, Ashish Arora
BACKGROUND: We have characterized two immunogenic proteins, Rv1197 and Rv1198, of the Esx-5 system of the ESAT-6 family of Mycobacterium tuberculosis H37Rv. METHODS: The complex formation between Rv1197 and Rv1198 was characterized by biophysical techniques. The reactivity of serum from TB patients towards these proteins was characterized by ELISA. Lymphocyte proliferation and cytokine induction were followed in restimulated splenocytes from immunized mice by using MTT assay and CBA flowcytometry, respectively...
October 14, 2016: Biochimica et Biophysica Acta
Leonardo A Gómez, Francisco I Alvarez, Pablo A Fernández, Manuel R Flores, Raúl E Molina, Roberto F Coloma, Angel A Oñate
Immunogenicity induced by recombinant plasmids based on the BAB1_0267 and BAB1_0270 open reading frames (ORFs) of Brucella abortus 2308 was evaluated. Bioinformatics analyses indicate that the BAB1_0267 and BAB1_0270 ORFs encode a protein with a SH3 domain and a Zn-dependent metalloproteinase, respectively. Both ORFs have important effects on intracellular survival and replication of B. abortus 2308, mediated via professional and non-professional phagocytic cells. Our results show that immunization with the recombinant plasmid based on the BAB1_0267 ORF significantly increases the production of IgG1, levels of IFN-γ and the lymphoproliferative response of splenocytes...
2016: Frontiers in Cellular and Infection Microbiology
Tetsuo Nakayama
The humoral and cellular immune responses of adaptive immunity are induced following immunization with effective vaccines. They induce functional cytokines and chemokines through the binding of vaccine components or adjuvants to innate immune receptors. Alum-adjuvanted vaccines induce local inflammatory nodules at injection sites, and the systemic and local production of the inflammatory cytokines, IL-1β, IL-6, and TNF-α, has been reported to occur three hours after vaccinations. Furthermore, G-CSF levels increase at injection sites...
October 13, 2016: Vaccine
Roger A Levy, Renato Guzman, Gilberto Castañeda-Hernández, Manuel Martinez-Vazquez, Guilherme Damian, Carlos Cara
Biologics are increasingly being used to modify the course of immune-mediated inflammatory diseases. Some main agents are monoclonal antibodies and a fusion-protein that target TNF. This group includes adalimumab, infliximab, certolizumab pegol, golimumab and etanercept. Although the efficacy of anti-TNFs is supported by numerous randomized clinical trials, their pharmacokinetics depend on many factors, in particular immunogenicity, which can cause marked and rapid clearance and a consequent decrease in efficacy...
October 14, 2016: Immunotherapy
Daniel Wendling, Frank Verhoeven, Xavier Guillot, Clément Prati
No abstract text is available yet for this article.
October 13, 2016: Expert Opinion on Drug Safety
Weili Yu, Tao Hu
Protein-based vaccines are of potential to deal with the severe situations posed by Mycobacterium tuberculosis (Mtb). Due to inherently poor immunogenicity of Mtb protein antigens, a potent immunostimulatory adjuvant is needed to enhance the cellular and humoral immune response to Mtb protein antigens. Inulin and chitosan (Cs) are polysaccharide adjuvants that can be used as achieve such an objective. The inulin-Cs conjugate (inulin-Cs) acted as a potent adjuvant through a synergistic interaction of inulin and Cs...
October 10, 2016: Molecular Pharmaceutics
Jae Hee Cheon
Remarkable advances have been made in the treatment of inflammatory bowel disease (IBD) since the introduction of anti-tumor necrosis factor (TNF)-α agents, especially for patients who are refractory to or cannot tolerate conventional therapies. Currently, infliximab, adalimumab, and golimumab are available in the East Asian medical market, and these agents have been shown to be effective for inducing and maintaining long-term remission of IBD. Despite their clinical benefits, anti-TNF therapy can also lead to increased vulnerability to infections, development of autoimmune diseases and malignancy, and decreased immunogenicity of vaccinations...
October 10, 2016: Journal of Gastroenterology and Hepatology
Pilar Requena, Edmilson Rui, Norma Padilla, Flor E Martínez-Espinosa, Maria Eugenia Castellanos, Camila Bôtto-Menezes, Adriana Malheiro, Myriam Arévalo-Herrera, Swati Kochar, Sanjay K Kochar, Dhanpat K Kochar, Alexandra J Umbers, Maria Ome-Kaius, Regina Wangnapi, Dhiraj Hans, Michela Menegon, Francesca Mateo, Sergi Sanz, Meghna Desai, Alfredo Mayor, Chetan C Chitnis, Azucena Bardají, Ivo Mueller, Stephen Rogerson, Carlo Severini, Carmen Fernández-Becerra, Clara Menéndez, Hernando Del Portillo, Carlota Dobaño
P. vivax infection during pregnancy has been associated with poor outcomes such as anemia, low birth weight and congenital malaria, thus representing an important global health problem. However, no vaccine is currently available for its prevention. Vir genes were the first putative virulent factors associated with P. vivax infections, yet very few studies have examined their potential role as targets of immunity. We investigated the immunogenic properties of five VIR proteins and two long synthetic peptides containing conserved VIR sequences (PvLP1 and PvLP2) in the context of the PregVax cohort study including women from five malaria endemic countries: Brazil, Colombia, Guatemala, India and Papua New Guinea (PNG) at different timepoints during and after pregnancy...
October 2016: PLoS Neglected Tropical Diseases
Xuefeng Wang, Li Li, Jun Wang, Liyang Dong, Yang Shu, Yong Liang, Liang Shi, Chengcheng Xu, Yuepeng Zhou, Yi Wang, Deyu Chen, Chaoming Mao
Helminth-derived products have recently been shown to prevent the development of inflammatory diseases in mouse models. However, most identified immunomodulators from helminthes are mixtures or macromolecules with potentially immunogenic side effects. We previously identified an immunomodulatory peptide called SJMHE1 from the HSP60 protein of Schistosoma japonicum. In this study, we assessed the ability of SJMHE1 to affect murine splenocytes and human peripheral blood mononuclear cells (PBMCs) stimulated by toll-like receptor (TLR) ligands in vitro and its treatment effect on mice with collagen-induced arthritis (CIA)...
September 28, 2016: Journal of Cellular and Molecular Medicine
Camille Planty, Corey P Mallett, Kevin Yim, Jorge C G Blanco, Marina Boukhvalova, Thomas March, Robbert van der Most, Eric Destexhe
An increased risk of narcolepsy following administration of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine (Pandemrix™) was described in children and adolescents in certain European countries. We investigated the potential effects of administration of the AS03-adjuvanted vaccine, non-adjuvanted vaccine antigen and AS03 Adjuvant System alone, on the central nervous system (CNS) in one-month-old cotton rats. Naïve or A(H1N1)pdm09 virus-primed animals received 2 or 3 intramuscular injections, respectively, of test article or saline at two-week intervals...
September 14, 2016: Human Vaccines & Immunotherapeutics
Kumar Avishek, Himanshu Kaushal, Sreenivas Gannavaram, Ranadhir Dey, Angamuthu Selvapandiyan, V Ramesh, Narender Singh Negi, Uma S Dubey, Hira L Nakhasi, Poonam Salotra
Currently no effective vaccine is available for human visceral leishmaniasis(VL) caused by Leishmania donovani. Previously, we showed that centrin1 and p27gene deleted live attenuated Leishmania parasites (LdCen1(-/-) and Ldp27(-/-)) are safe, immunogenic and protective in animal models. Here, to assess the correlates of protection, we evaluated immune responses induced by LdCen1(-/-) and Ldp27(-/-) in human blood samples obtained from healthy, healed VL (HVL), post kala-azar dermal leishmaniasis(PKDL) and VL subjects...
2016: Scientific Reports
Sefayet Karaca, Ersoy Civelek, Mehmet Karaca, Umit M Sahiner, Riza K Ozgul, Can N Kocabas, Renato Polimanti, Bülent E Sekerel
To dissect the role of immunogenetics in allergy and asthma, we performed a phenome-wide association study in 974 Turkish children selected from a cross-sectional study conducted using ISAAC (International Study of Asthma and Allergies in Children) Phase II tools. We investigated 9 loci involved in different immune functions (ADAM33, ADRB2, CD14, IL13, IL4, IL4R, MS4A2, SERPINE1, and TNF) with respect to 116 traits assessed through blood tests, hypertonic saline challenge tests, questionnaires, and skin prick tests...
2016: Scientific Reports
Laura Bernal, Abigail Alvarado-Vázquez, David Wilson Ferreira, Candler A Paige, Cristina Ulecia-Morón, Bailey Hill, Marina Caesar, E Alfonso Romero-Sandoval
Macrophages orchestrate the initiation and resolution of inflammation by producing pro- and anti-inflammatory products. An imbalance in these mediators may originate from a deficient or excessive immune response. Therefore, macrophages are valid therapeutic targets to restore homeostasis under inflammatory conditions. We hypothesize that a specific mannosylated nanoparticle effectively induces gene expression in human macrophages under inflammatory conditions without undesirable immunogenic responses. THP-1 macrophages were challenged with lipopolysaccharide (LPS, 5μg/mL)...
September 5, 2016: Immunobiology
R Talotta, A Berzi, F Atzeni, D Dell'Acqua, P Sarzi Puttini, D Trabattoni
The aim of this study was to determine the prevalence of T helper 9 (Th9) lymphocytes in rheumatoid arthritis (RA) patients and to identify a possible association between the percentage of Th9 and the discontinuation of a biological treatment with an anti-tumor necrosis factor (TNF) (infliximab). We collected peripheral blood mononuclear cells (PBMCs) from 55 consecutive RA outpatients and 10 healthy controls. Among RA patients, 15 were not receiving any immunosuppressive drug, 20 were successfully treated with infliximab and 20 discontinued infliximab because of adverse events or inefficacy and were treated with other biological agents...
2016: Reumatismo
Xiu Fen Liu, Laiman Xiang, Qi Zhou, Jean-Philippe Carralot, Marco Prunotto, Gerhard Niederfellner, Ira Pastan
RG7787 is a mesothelin-targeted immunotoxin designed to have low-immunogenicity, high-cytotoxic activity and fewer side effects. RG7787 kills many types of mesothelin-expressing cancer cells lines and causes tumor regressions in mice. Safety and immunogenicity of RG7787 is now being assessed in a phase I trial. To enhance the antitumor activity of RG7787, we screened for clinically used drugs that can synergize with RG7787. Actinomycin D is a potent transcription inhibitor that is used for treating several cancers...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
Sebastian Felgner, Michael Frahm, Dino Kocijancic, Manfred Rohde, Denitsa Eckweiler, Agata Bielecka, Emilio Bueno, Felipe Cava, Wolf-Rainer Abraham, Roy Curtiss, Susanne Häussler, Marc Erhardt, Siegfried Weiss
UNLABELLED: Recombinant attenuated Salmonella enterica serovar Typhimurium strains are believed to act as powerful live vaccine carriers that are able to elicit protection against various pathogens. Auxotrophic mutations, such as a deletion of aroA, are commonly introduced into such bacteria for attenuation without incapacitating immunostimulation. In this study, we describe the surprising finding that deletion of aroA dramatically increased the virulence of attenuated Salmonella in mouse models...
2016: MBio
Juan Pablo Mackern-Oberti, Evelyn L Jara, Claudia A Riedel, Alexis M Kalergis
Hormonal homeostasis is crucial for keeping a competent and healthy immune function. Several hormones can modulate the function of various immune cells such as dendritic cells (DCs) by influencing the initiation of the immune response and the maintenance of peripheral tolerance to self-antigens. Hormones, such as estrogens, prolactin, progesterone and glucocorticoids may profoundly affect DCs differentiation, maturation and function leading to either a pro-inflammatory or an anti-inflammatory (or tolerogenic) phenotype...
September 1, 2016: Archivum Immunologiae et Therapiae Experimentalis
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