scholarly journals Chitosan nanoparticle formulation attenuates poly (I:C) induced innate immune responses against inactivated virus vaccine in Atlantic salmon (Salmo salar)

Author(s):  
Adriana Magalhães Santos Andresen ◽  
Tor Gjøen
2016 ◽  
Vol 48 (5) ◽  
pp. 2495-2515 ◽  
Author(s):  
Christoforos Panicos Metochis ◽  
Vivian O Crampton ◽  
Kari Ruohonen ◽  
Adel El-Mowafi ◽  
John Gordon Bell ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7461
Author(s):  
Claire K. Holley ◽  
Edward Cedrone ◽  
Duncan Donohue ◽  
Barry W. Neun ◽  
Daniela Verthelyi ◽  
...  

Understanding, predicting, and minimizing the immunogenicity of peptide-based therapeutics are of paramount importance for ensuring the safety and efficacy of these products. The so-called anti-drug antibodies (ADA) may have various clinical consequences, including but not limited to the alteration in the product’s distribution, biological activity, and clearance profiles. The immunogenicity of biotherapeutics can be influenced by immunostimulation triggered by the presence of innate immune response modulating impurities (IIRMIs) inadvertently introduced during the manufacturing process. Herein, we evaluate the applicability of several in vitro assays (i.e., complement activation, leukocyte proliferation, and cytokine secretion) for the screening of innate immune responses induced by ten common IIRMIs (Bacillus subtilis flagellin, FSL-1, zymosan, ODN2006, poly(I:C) HMW, poly(I:C) LMW, CLO75, MDP, ODN2216, and Escherichia coli O111:B4 LPS), and a model biotherapeutic Forteo™ (teriparatide). Our study identifies cytokine secretion from healthy human donor peripheral blood mononuclear cells (PBMC) as a sensitive method for the in vitro monitoring of innate immune responses to individual IIRMIs and teriparatide (TP). We identify signature cytokines, evaluate both broad and narrow multiplex cytokine panels, and discuss how the assay logistics influence the performance of this in vitro assay.


2019 ◽  
Vol 91 ◽  
pp. 454-455
Author(s):  
Leidy Lagos ◽  
Jon Øvrum Hansen ◽  
Cristina Tomás-Almenar ◽  
Byron Morales ◽  
Peng Lei ◽  
...  

2009 ◽  
Vol 297 (3) ◽  
pp. L530-L537 ◽  
Author(s):  
Philip R. Cooper ◽  
Roberta Lamb ◽  
Nicole D. Day ◽  
Patrick J. Branigan ◽  
Radhika Kajekar ◽  
...  

Respiratory infections exacerbate chronic lung diseases promoting airway inflammation and hyperreactivity. Toll-like receptor 3 (TLR3) recognizes viral double-stranded (ds) RNA such as polyinosinic-polycytidylic acid [poly(I:C)] and stimulates innate immune responses. The objective of this study was to test the hypothesis that dsRNA promotes lung inflammation and alters airway responsiveness to cholinergic and β-adrenergic receptor agonists in human lung slices. Human airway smooth muscle (ASM) was incubated for 24 h in poly(I:C) ± TNFα and a TLR3 monoclonal antibody. Precision-cut lung slices (PCLS; 250-μm thickness) from healthy human lungs containing a small airway were incubated in 0, 10, or 100 μg/ml poly(I:C) for 24 h. Intravital microscopy of lung slices was used to quantify contractile and relaxation responsiveness to carbachol and isoproterenol, respectively. Supernatants of ASM and PCLS were analyzed for cytokine secretion using a 25-multiplex bead assay. In human ASM, poly(I:C) (0.5 μg/ml) increased macrophage inflammatory protein-1α (MIP-1α) and RANTES that was prevented by a TLR3 monoclonal receptor antibody. Incubation of human PCLS with poly(I:C) (10 and 100 μg/ml) had little effect on the log EC50 or maximum drug effect (Emax) for contraction and relaxation in response to carbachol and isoproterenol, respectively. The responsiveness of the same human PCLS to poly(I:C) incubation was confirmed by the robust increase in chemokines and cytokines. In separate experiments, incubation of PCLS with IL-13 or TNFα (100 ng/ml) increased airway sensitivity to carbachol. Poly(I:C) promotes inflammatory mediator release that was not associated with enhanced bronchoconstriction or attenuated bronchodilation in normal healthy human lung slices. Transduction at the TLR3 initiated by dsRNA stimulates downstream innate immune responses.


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