Pollinex® Quattro Ragweed: safety evaluation of a new allergy vaccine adjuvanted with monophosphoryl lipid A (MPL®) for the treatment of ragweed pollen allergy

2007 ◽  
Vol 27 (4) ◽  
pp. 399-409 ◽  
Author(s):  
Paul Baldrick ◽  
Derek Richardson ◽  
Stefan R. Woroniecki ◽  
Beverley Lees
Keyword(s):  
Lipid A ◽  
Safety Evaluation ◽  
Pollen Allergy ◽  
Ragweed Pollen ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Allergy Vaccine

Safety Evaluation of Monophosphoryl Lipid A (MPL): An Immunostimulatory Adjuvant

2002 ◽  
Vol 35 (3) ◽  
pp. 398-413 ◽  
Author(s):  
Paul Baldrick ◽  
Derek Richardson ◽  
Gary Elliott ◽  
Alan W. Wheeler
Keyword(s):  
Lipid A ◽  
Safety Evaluation ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid

Long-term effect of monophosphoryl lipid A adjuvanted specific immunotherapy in patients with grass pollen allergy

Immunotherapy ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 529-536 ◽  
Author(s):  
Stefan Zielen ◽  
Jennis Gabrielpillai ◽  
Eva Herrmann ◽  
Johannes Schulze ◽  
Ralf Schubert ◽  
...  
Keyword(s):  
Grass Pollen ◽  
Lipid A ◽  
Specific Immunotherapy ◽  
Pollen Allergy ◽  
Term Effect ◽  
Grass Pollen Allergy ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Long Term Effect

Monophosphoryl lipid A: an effective adjuvant for potentiating mucosal immune responses

1999 ◽  
Vol 5 (3) ◽  
pp. 181-182 ◽  
Author(s):  
Suzanne M. Michalek ◽  
Noel K. Childers ◽  
Terry Greenway ◽  
George Hajishengallis ◽  
J. Terry Ulrich
Keyword(s):  
Immune Responses ◽  
Lipid A ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Mucosal Immune Responses

scholarly journals Monophosphoryl lipid A induces protection against LPS in medullary thick ascending limb through a TLR4-TRIF-PI3K signaling pathway

2017 ◽  
Vol 313 (1) ◽  
pp. F103-F115 ◽  
Author(s):  
Bruns A. Watts ◽  
Thampi George ◽  
Edward R. Sherwood ◽  
David W. Good
Keyword(s):  
Bacterial Infections ◽  
Lipid A ◽  
Thick Ascending Limb ◽  
Akt Inhibitor ◽  
Erk Activation ◽  
Akt Phosphorylation ◽  
Medullary Thick Ascending Limb ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid

Monophosphoryl lipid A (MPLA) is a detoxified derivative of LPS that induces tolerance to LPS and augments host resistance to bacterial infections. Previously, we demonstrated that LPS inhibits [Formula: see text] absorption in the medullary thick ascending limb (MTAL) through a basolateral Toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-ERK pathway. Here we examined whether pretreatment with MPLA would attenuate LPS inhibition. MTALs from rats were perfused in vitro with MPLA (1 µg/ml) in bath and lumen or bath alone for 2 h, and then LPS was added to (and MPLA removed from) the bath solution. Pretreatment with MPLA eliminated LPS-induced inhibition of [Formula: see text] absorption. In MTALs pretreated with MPLA plus a phosphatidylinositol 3-kinase (PI3K) or Akt inhibitor, LPS decreased [Formula: see text] absorption. MPLA increased Akt phosphorylation in dissected MTALs. The Akt activation was eliminated by a PI3K inhibitor and in MTALs from TLR4−/−or Toll/IL-1 receptor domain-containing adaptor-inducing IFN-β (TRIF)−/−mice. The effect of MPLA to prevent LPS inhibition of [Formula: see text] absorption also was TRIF dependent. Pretreatment with MPLA prevented LPS-induced ERK activation; this effect was dependent on PI3K. MPLA alone had no effect on [Formula: see text] absorption, and MPLA pretreatment did not prevent ERK-mediated inhibition of [Formula: see text] absorption by aldosterone, consistent with MPLA's low toxicity profile. These results demonstrate that pretreatment with MPLA prevents the effect of LPS to inhibit [Formula: see text] absorption in the MTAL. This protective effect is mediated directly through MPLA stimulation of a TLR4-TRIF-PI3K-Akt pathway that prevents LPS-induced ERK activation. These studies identify detoxified TLR4-based immunomodulators as novel potential therapeutic agents to prevent or treat renal tubule dysfunction in response to bacterial infections.

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