scholarly journals Lipid A-Mediated Bacterial–Host Chemical Ecology: Synthetic Research of Bacterial Lipid As and Their Development as Adjuvants

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6294
Author(s):  
Atsushi Shimoyama ◽  
Koichi Fukase
Keyword(s):  
Chemical Ecology ◽  
Structural Changes ◽  
Lipid A ◽  
Active Principle ◽  
Functional Evaluation ◽  
Vaccine Adjuvants ◽  
Bacterial Host ◽  
Adjuvant Effect ◽  
Biological Phenomena ◽  
Low Toxicity

Gram-negative bacterial cell surface component lipopolysaccharide (LPS) and its active principle, lipid A, exhibit immunostimulatory effects and have the potential to act as adjuvants. However, canonical LPS acts as an endotoxin by hyperstimulating the immune response. Therefore, LPS and lipid A must be structurally modified to minimize their toxic effects while maintaining their adjuvant effect for application as vaccine adjuvants. In the field of chemical ecology research, various biological phenomena occurring among organisms are considered molecular interactions. Recently, the hypothesis has been proposed that LPS and lipid A mediate bacterial–host chemical ecology to regulate various host biological phenomena, mainly immunity. Parasitic and symbiotic bacteria inhabiting the host are predicted to possess low-toxicity immunomodulators due to the chemical structural changes of their LPS caused by co-evolution with the host. Studies on the chemical synthesis and functional evaluation of their lipid As have been developed to test this hypothesis and to apply them to low-toxicity and safe adjuvants.

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.

scholarly journals POLOXAMER 407 GEL FOR TOPICAL ADMINISTRATION: INFLUENCE OF ACETIC ACID AND DEMINERALIZED WATER ON THE BEHAVIOR OF THE GEL OBTAINED

2019 ◽  
Vol 7 (6) ◽  
pp. 270-275
Author(s):  
Dally Li ◽  
Lia Gja ◽  
N'guessan A ◽  
Aka Any-Grah ◽  
Tuo A ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Ground State ◽  
Topical Administration ◽  
Deionized Water ◽  
Poloxamer 407 ◽  
Active Principle ◽  
Gelling Temperature ◽  
Demineralized Water ◽  
Low Toxicity ◽  
Evaluation Parameters

Background: Poloxamers are low-toxicity copolymers whose aqueous solutions can pass reversibly from the ground state to the gel state at temperatures approaching body temperature, which is of interest for their use as a reservoir system of active principle. Understand the effect of the type of solvent on the rheological characteristics of the gel obtained. Methods: Various formulations of Poloxamer 407 gel at 16% and 17,5% were prepared and evaluated successively in acetic acid and demineralised water. The main evaluation parameters were the gelling temperature (T gel) and the concentration of these different solvents. Results: The T (gel) at 16% F127 in demineralised water and 0.1M acetic acid was 27º ± 0.3 and 17.5% at 25º to 29ºC ± 0.1. in 0.1M and 16 % acetic acid, there is no marked gelation. At 17.5% F127 in acetic acid, gelationwas observed and the Tgel was higher than with F127 in deionized water. Conclusion: The gelation process is favored by increasing the concentration of  F127 and is substantially disadvantaged by 0.1M acetic acid.

scholarly journals Combining Monophosphoryl Lipid A (MPL), CpG Oligodeoxynucleotide (ODN), and QS-21 Adjuvants Induces Strong and Persistent Functional Antibodies and T Cell Responses against Cell-Traversal Protein for Ookinetes and Sporozoites (CelTOS) ofPlasmodium falciparumin BALB/c Mice

2019 ◽  
Vol 87 (6) ◽  
Author(s):  
Sakineh Pirahmadi ◽  
Sedigheh Zakeri ◽  
Akram A. Mehrizi ◽  
Navid D. Djadid ◽  
Abbas-Ali Raz ◽  
...  
Keyword(s):  
Lipid A ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vaccine Adjuvants ◽  
Content Type ◽  
Quillaja Saponaria ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Cpg Oligodeoxynucleotide ◽  
Membrane Feeding ◽  
Functional Antibodies

ABSTRACTPlasmodium falciparumcell-traversal protein for ookinetes and sporozoites (PfCelTOS) is an advanced vaccine candidate that has a crucial role in the traversal of the malaria parasite in both mosquito and mammalian hosts. As recombinant purified proteins are normally poor immunogens, they require to be admixed with an adjuvant(s); therefore, the objective of the present study was to evaluate the capacity of different vaccine adjuvants, monophosphoryl lipid A (MPL), CpG, andQuillaja saponariaMolina fraction 21 (QS-21), alone or in combination (MCQ [MPL/CpG/QS-21]), to enhance the immunogenicity ofEscherichia coli-expressed PfCelTOS in BALB/c mice. This goal was achieved by the assessment of anti-PfCelTOS IgG antibodies (level, titer, IgG isotype profile, avidity, and persistence) and extracellular Th1 cytokines using an enzyme-linked immunosorbent assay (ELISA) on postimmunized BALB/c mouse sera and PfCelTOS-stimulated splenocytes, respectively. Also, an assessment of the transmission-reducing activity (TRA) of anti-PfCelTOS obtained from different vaccine groups was carried out in femaleAnopheles stephensimosquitoes by using a standard membrane feeding assay (SMFA). In comparison to PfCelTOS alone, administration of PfCelTOS with three distinct potent Th1 adjuvants in vaccine mouse groups showed enhancement and improvement of PfCelTOS immunogenicity that generated more bias toward a Th1 response with significantly enhanced titers and avidity of the anti-PfCelTOS responses that could impair ookinete development inA. stephensi. However, immunization of mice with PfCelTOS with MCQ mixture adjuvants resulted in the highest levels of induction of antibody titers, avidity, and inhibitory antibodies in oocyst development (88%/26.7% reductions in intensity/prevalence) inA. stephensi. It could be suggested that adjuvant combinations with different mechanisms stimulate better functional antibody responses than adjuvants individually against challenging diseases such as malaria.

scholarly journals Gamma Interferon and Monophosphoryl Lipid A-Trehalose Dicorynomycolate Are Efficient Adjuvants for Mycobacterium tuberculosis Multivalent Acellular Vaccine

2005 ◽  
Vol 73 (1) ◽  
pp. 250-257 ◽  
Author(s):  
Avi-Hai Hovav ◽  
Yolanta Fishman ◽  
Herve Bercovier
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Lipid A ◽  
Protective Efficacy ◽  
Gamma Interferon ◽  
No Production ◽  
Adjuvant Effect ◽  
Recombinant Antigens ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Ifn Γ

ABSTRACT In this study, we examined the immunogenicity and protective efficacy of six immunodominant Mycobacterium tuberculosis recombinant antigens (85B, 38kDa, ESAT-6, CFP21, Mtb8.4, and 16kDa) in a multivalent vaccine preparation (6Ag). Gamma interferon (IFN-γ) and monophosphoryl lipid A-trehalose dicorynomycolate (Ribi) adjuvant systems were used separately or in combination for immunization with the recombinant antigens. Our results demonstrate that immunization of mice with Ribi emulsified antigens in the presence of IFN-γ (Ribi+6Ag+IFN-γ) resulted after challenge with a virulent M. tuberculosis strain in a significant reduction in the CFU counts that was comparable to that achieved with the BCG vaccine (∼0.9-log protection). Antigen-specific immunoglobulin G (IgG) titers in the Ribi+6Ag+IFN-γ-immunized mice were lower than in mice immunized with Ribi+6Ag and were oriented toward a Th1-type response, as confirmed by elevated IgG2a levels. In addition, splenocyte proliferation, IFN-γ secretion, and NO production were significantly higher in splenocytes derived from Ribi+6Ag+IFN-γ-immunized mice, whereas IL-10 secretion was decreased. These findings confirm the induction of a strong cellular immunity in the vaccinated mice that correlates well with their enhanced resistance to M. tuberculosis. The adjuvant effect of IFN-γ was dose dependent. A dose of 5 μg of IFN-γ per mouse per immunization gave optimal protection, whereas lower or higher amounts (0.5 or 50 μg/ mouse) of IFN-γ failed to enhance protection.

scholarly journals Structural Modification of Lipopolysaccharide Conferred by mcr-1 in Gram-Negative ESKAPE Pathogens

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Yi-Yun Liu ◽  
Courtney E. Chandler ◽  
Lisa M. Leung ◽  
Christi L. McElheny ◽  
Roberta T. Mettus ◽  
...  
Keyword(s):  
Structural Changes ◽  
Lipid A ◽  
Colistin Resistance ◽  
Gram Negative ◽  
Content Type ◽  
Clinical Strains ◽  
E Coli ◽  
The Family ◽  
Phosphoethanolamine Transferases ◽  
Eskape Pathogens

ABSTRACT mcr-1 was initially reported as the first plasmid-mediated colistin resistance gene in clinical isolates of Escherichia coli and Klebsiella pneumoniae in China and has subsequently been identified worldwide in various species of the family Enterobacteriaceae. mcr-1 encodes a phosphoethanolamine transferase, and its expression has been shown to generate phosphoethanolamine-modified bis-phosphorylated hexa-acylated lipid A in E. coli. Here, we investigated the effects of mcr-1 on colistin susceptibility and on lipopolysaccharide structures in laboratory and clinical strains of the Gram-negative ESKAPE (Enterococcus faecium, Staphylococcus aureus, K. pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens, which are often treated clinically by colistin. The effects of mcr-1 on colistin resistance were determined using MIC assays of laboratory and clinical strains of E. coli, K. pneumoniae, A. baumannii, and P. aeruginosa. Lipid A structural changes resulting from MCR-1 were analyzed by mass spectrometry. The introduction of mcr-1 led to colistin resistance in E. coli, K. pneumoniae, and A. baumannii but only moderately reduced susceptibility in P. aeruginosa. Phosphoethanolamine modification of lipid A was observed consistently for all four species. These findings highlight the risk of colistin resistance as a consequence of mcr-1 expression among ESKAPE pathogens, especially in K. pneumoniae and A. baumannii. Furthermore, the observation that lipid A structures were modified despite only modest increases in colistin MICs in some instances suggests more sophisticated surveillance methods may need to be developed to track the dissemination of mcr-1 or plasmid-mediated phosphoethanolamine transferases in general.

Low toxicity signaling by monophosphoryl Lipid A

Cytokine ◽  
2009 ◽  
Vol 48 (1-2) ◽  
pp. 129
Author(s):  
Thomas C. Mitchell ◽  
Caglar Cekic ◽  
Carolyn R. Casella ◽  
Chelsea A. Eaves
Keyword(s):  
Lipid A ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Low Toxicity
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