scholarly journals A Fusion Protein Consisting of the Vaccine Adjuvant Monophosphoryl Lipid A and the Allergen Ovalbumin Boosts Allergen-Specific Th1, Th2, and Th17 ResponsesIn Vitro

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Stefan Schülke ◽  
Lothar Vogel ◽  
Ann-Christine Junker ◽  
Kay-Martin Hanschmann ◽  
Adam Flaczyk ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Lipid A ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Strong Stimulation ◽  
Tlr Agonist ◽  
Allergy Treatment ◽  
Tlr4 Ligand ◽  
Th17 Cytokine ◽  
Stimulation Of

Background. The detoxified TLR4-ligand Monophosphoryl Lipid A (MPLA) is the first approved TLR-agonist used as adjuvant in licensed vaccines but has not yet been explored as part of conjugated vaccines.Objective. To investigate the immune-modulating properties of a fusion protein consisting of MPLA and Ovalbumin (MPLA : Ova).Results. MPLA and Ova were chemically coupled by stable carbamate linkage. MPLA : Ova was highly pure without detectable product-related impurities by either noncoupled MPLA or Ova. Light scattering analysis revealed MPLA : Ova to be aggregated. Stimulation of mDC and mDC : DO11.10 CD4+TC cocultures showed a stronger activation of both mDC and Ova-specific DO11.10 CD4+TC by MPLA : Ova compared to the mixture of both components. MPLA : Ova induced both strong proinflammatory (IL-1β, IL-6, and TNF-α) and anti-inflammatory (IL-10) cytokine responses from mDCs while also boosting allergen-specific Th1, Th2, and Th17 cytokine secretion.Conclusion. Conjugation of MPLA and antigen enhanced the immune response compared to the mixture of both components. Due to the nonbiased boost of Ova-specific Th2 and Th17 responses while also inducing Th1 responses, this fusion protein may not be a suitable vaccine candidate for allergy treatment but may hold potential for the treatment of other diseases that require a strong stimulation of the host’s immune system (e.g., cancer).

Immunogenicity & reactogenicity of a recombinant HPV6 fusion protein vaccine adjuvanted with monophosphoryl lipid A

1997 ◽  
Vol 25 (2) ◽  
pp. 274S-274S
Author(s):  
STEPHEN THOMPSON ◽  
MARIE DAVIES ◽  
TERRY O'NEILL ◽  
FINN HOLDING ◽  
ALISON MANN ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Lipid A ◽  
Protein Vaccine ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid

scholarly journals MyD88-Dependent SHIP1 Regulates Proinflammatory Signaling Pathways in Dendritic Cells after Monophosphoryl Lipid A Stimulation of TLR4

2011 ◽  
Vol 186 (7) ◽  
pp. 3858-3865 ◽  
Author(s):  
Caglar Cekic ◽  
Carolyn R. Casella ◽  
Duygu Sag ◽  
Frann Antignano ◽  
Joseph Kolb ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Signaling Pathways ◽  
Lipid A ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Stimulation Of

scholarly journals Lactoferrin-monophosphoryl lipid A complex enhances immunity of mice to Plesiomonas shigelloides CNCTC 138/92.

2008 ◽  
Vol 55 (1) ◽  
pp. 91-96 ◽  
Author(s):  
Grzegorz Chodaczek ◽  
Michal Zimecki ◽  
Jolanta Lukasiewicz ◽  
Czesław Lugowski
Keyword(s):  
Immune Response ◽  
Lipid A ◽  
Adjuvant Effect ◽  
Plesiomonas Shigelloides ◽  
Monophosphoryl Lipid A ◽  
Specific Serum ◽  
Monophosphoryl Lipid ◽  
Serum Iga ◽  
Cellular Immune ◽  
Stimulation Of

Our previous study showed the efficacy of lactoferrin-monophosphoryl lipid A isolated from Hafnia alvei LPS complex (LF-MPL(H.a.)) as an adjuvant in stimulation of humoral and cellular immune response in mice to conventional antigens and a lower pyrogenicity of the complex as compared with MPL(H.a.) alone. In the present investigation we demonstrated that LF-MPL(H.a.) complex enhanced the immunity of BALB/c mice immunized with Plesiomonas shigelloides CNCTC 138/92 bacterial vaccine, against P. shigelloides infection. The adjuvant effect was evidenced by a significant increase of the antigen-specific serum IgG, IgG(2a), and IgG(1) and elevation of antigen-specific serum IgA concentrations. In addition, application of the adjuvant facilitated better clearance of the bacteria in spleens and livers of infected mice when compared with MPL(H.a.) alone. These features of the new adjuvant may predispose it for vaccination protocols in humans.

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.

Enhanced immunogenicity of a recombinant genital warts vaccine adjuvanted with monophosphoryl lipid A

Vaccine ◽  
1998 ◽  
Vol 16 (20) ◽  
pp. 1993-1999 ◽  
Author(s):  
H.S.G Thompson ◽  
M.L Davies ◽  
M.J Watts ◽  
A.E Mann ◽  
F.P Holding ◽  
...  
Keyword(s):  
Lipid A ◽  
Genital Warts ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid
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