The Impact on Allergy-Related Cells of a Birch Pollen Allergoid, with and without Monophosphoryl Lipid A, in Comparison with the Native Equivalent

2017 ◽  
Vol 172 (1) ◽  
pp. 20-26 ◽  
Author(s):  
Margitta Worm ◽  
Dennis Ernst ◽  
Markus Kraller ◽  
Magda Babina
Keyword(s):  
Lipid A ◽  
Birch Pollen ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
The Impact

scholarly journals A Comparison of Intramuscular and Subcutaneous Administration of LigA Subunit Vaccine Adjuvanted with Neutral Liposomal Formulation Containing Monophosphoryl Lipid A and QS21

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 494 ◽  
Author(s):  
Teerasit Techawiwattanaboon ◽  
Christophe Barnier-Quer ◽  
Tanapat Palaga ◽  
Alain Jacquet ◽  
Nicolas Collin ◽  
...  
Keyword(s):  
Survival Rate ◽  
Subunit Vaccine ◽  
Lipid A ◽  
Protective Efficacy ◽  
Protein A ◽  
Subcutaneous Administration ◽  
Protective Effects ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
The Impact

Leptospirosis vaccines with higher potency and reduced adverse effects are needed for human use. The carboxyl terminal domain of leptospiral immunoglobulin like protein A (LigAc) is currently the most promising candidate antigen for leptospirosis subunit vaccine. However, LigAc-based vaccines were unable to confer sterilizing immunity against Leptospira infection in animal models. Several factors including antigen properties, adjuvant, delivery system, and administration route need optimization to maximize vaccine efficacy. Our previous report demonstrated protective effects of the recombinant LigAc (rLigAc) formulated with liposome-based adjuvant, called LMQ (neutral liposome combined with monophosphoryl lipid A and Quillaja saponaria fraction 21) in hamsters. This study aimed to evaluate the impact of two commonly used administration routes, intramuscular (IM) and subcutaneous (SC), on immunogenicity and protective efficacy of rLigAc-LMQ administrated three times at 2-week interval. Two IM vaccinations triggered significantly higher levels of total anti-rLigAc IgG than two SC injections. However, comparable IgG titers and IgG2/IgG1 ratio was observed for both routes after the third immunization. The route of vaccine administration did not influence the survival rate (60%) and renal colonization against lethal Leptospira challenge. Importantly, the kidneys of IM group showed no pathological lesions while the SC group showed mild damage. In conclusion, IM vaccination with rLigAc-LMQ not only elicited faster antibody production but also protected from kidney damage following leptospiral infection better than SC immunization. However, both tested routes did not influence protective efficacy in terms of survival rate and the level of renal colonization.

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

scholarly journals TLR4 Ligands Augment Antigen-Specific CD8+ T Lymphocyte Responses Elicited by a Viral Vaccine Vector

2010 ◽  
Vol 84 (19) ◽  
pp. 10413-10419 ◽  
Author(s):  
Elizabeth G. Rhee ◽  
R. Phelps Kelley ◽  
Isha Agarwal ◽  
Diana M. Lynch ◽  
Annalena La Porte ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Lipid A ◽  
Viral Vector ◽  
Recombinant Adenovirus ◽  
Poly I:C ◽  
Vaccine Adjuvants ◽  
Monophosphoryl Lipid A ◽  
Viral Vaccine ◽  
Lymphocyte Responses ◽  
The Impact

ABSTRACT Toll-like receptor (TLR) ligands are critical activators of innate immunity and are being developed as vaccine adjuvants. However, their utility in conjunction with viral vector-based vaccines remains unclear. In this study, we evaluated the impact of a variety of TLR ligands on antigen-specific CD8+ T lymphocyte responses elicited by a recombinant adenovirus serotype 26 (rAd26) vector expressing simian immunodeficiency virus Gag in mice. The TLR3 ligand poly(I:C) suppressed Gag-specific cellular immune responses, whereas the TLR4 ligands lipopolysaccharide and monophosphoryl lipid A substantially augmented the magnitude and functionality of these responses by a MyD88- and TRIF-dependent mechanism. These data demonstrate that TLR ligands can modulate the immunogenicity of viral vaccine vectors both positively and negatively. Moreover, these findings suggest the potential utility of TLR4 ligands as adjuvants for rAd vector-based vaccines.

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