scholarly journals Chemical and Immunological Characteristics of Aluminum-Based, Oil-Water Emulsion, and Bacterial-Origin Adjuvants

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Susana Martiñón ◽  
Angel Cisneros ◽  
Sergio Villicaña ◽  
Ricardo Hernández-Miramontes ◽  
Edgar Mixcoha ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Lipid A ◽  
Humoral Response ◽  
Main Concern ◽  
Protein Antigens ◽  
Water Emulsion ◽  
Bacterial Origin ◽  
Monophosphoryl Lipid A ◽  
Oil Water

Adjuvants are a diverse family of substances whose main objective is to increase the strength, quality, and duration of the immune response caused by vaccines. The most commonly used adjuvants are aluminum-based, oil-water emulsion, and bacterial-origin adjuvants. In this paper, we will discuss how the election of adjuvants is important for the adjuvant-mediated induction of immunity for different types of vaccines. Aluminum-based adjuvants are the most commonly used, the safest, and have the best efficacy, due to the triggering of a strong humoral response, albeit generating a weak induction of cell-mediated immune response. Freund’s adjuvant is the most widely used oil-water emulsion adjuvant in animal trials; it stimulates inflammation and causes aggregation and precipitation of soluble protein antigens that facilitate the uptake by antigen-presenting cells (APCs). Adjuvants of bacterial origin, such as flagellin,E. colimembranes, and monophosphoryl lipid A (MLA), are known to potentiate immune responses, but their safety and risks are the main concern of their clinical use. This minireview summarizes the mechanisms that classic and novel adjuvants produce to stimulate immune responses.

scholarly journals Coupled complementation of immune response genes controlling responsiveness to the H-2.2 alloantigen.

1977 ◽  
Vol 146 (2) ◽  
pp. 571-578 ◽  
Author(s):  
M E Dorf ◽  
J H Stimpfling
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Humoral Response ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
F1 Hybrids ◽  
Gene Control ◽  
Low Responder ◽  
Resistant Strains ◽  
High Level

The ability of various B10 congenic resistant strains to respond to the alloantigen H-2.2 was tested. High and low antibody-producing strains were distinguished by their anti-H-2.2 hemagglutinating respones. However, these strains do not differ in their ability to respond to these antigenic differences in the mixed lymphocyte culture. The humoral response to the H-2.2 alloantigen was shown to be controlled by two interacting genes localized within the H-2 complex. Thus, F1 hybrids prepared between parental low responder strains could yield high level immune responses. In addition, strains bearing recombinant H-2 haplotypes were used to map the two distinct genes controlling the immune response. The alleles at each locus were shown to be highly polymorphic as evidenced by the asymmetric complementation patterns observed. The restricted interactions of specific alleles was termed coupled complementation. The significance of the results in the terms of mechanisms of Ir gene control are discussed.

scholarly journals TRAF6-IRF5 kinetics, TRIF, and biophysical factors drive synergistic innate responses to particle-mediated MPLA-CpG co-presentation

2021 ◽  
Vol 7 (3) ◽  
pp. eabd4235
Author(s):  
P. Pradhan ◽  
R. Toy ◽  
N. Jhita ◽  
A. Atalis ◽  
B. Pandey ◽  
...  
Keyword(s):  
Immune Responses ◽  
Molecular Mechanisms ◽  
Lipid A ◽  
Critical Role ◽  
Mouse Bone Marrow ◽  
Biophysical Properties ◽  
Gm Csf ◽  
Monophosphoryl Lipid A ◽  
Integrated Response ◽  
Particulate Carriers

Innate immune responses to pathogens are driven by co-presentation of multiple pathogen-associated molecular patterns (PAMPs). Combinations of PAMPs can trigger synergistic immune responses, but the underlying molecular mechanisms of synergy are poorly understood. Here, we used synthetic particulate carriers co-loaded with monophosphoryl lipid A (MPLA) and CpG as pathogen-like particles (PLPs) to dissect the signaling pathways responsible for dual adjuvant immune responses. PLP-based co-delivery of MPLA and CpG to GM-CSF–driven mouse bone marrow–derived antigen-presenting cells (BM-APCs) elicited synergistic interferon-β (IFN-β) and interleukin-12p70 (IL-12p70) responses, which were strongly influenced by the biophysical properties of PLPs. Mechanistically, we found that MyD88 and interferon regulatory factor 5 (IRF5) were necessary for IFN-β and IL-12p70 production, while TRIF signaling was required for the synergistic response. Both the kinetics and magnitude of downstream TRAF6 and IRF5 signaling drove the synergy. These results identify the key mechanisms of synergistic Toll-like receptor 4 (TLR4)–TLR9 co-signaling in mouse BM-APCs and underscore the critical role of signaling kinetics and biophysical properties on the integrated response to combination adjuvants.

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 Induction of rheumatoid antibodies in the mouse. Regulated production of autoantibody in the secondary humoral response.

1983 ◽  
Vol 158 (2) ◽  
pp. 529-545 ◽  
Author(s):  
D A Nemazee ◽  
V L Sato
Keyword(s):  
Immune Response ◽  
Humoral Response ◽  
Secondary Immune Response ◽  
Protein Antigens ◽  
Common Component ◽  
Igg1 Antibody ◽  
Order Of Magnitude

A/J mice were found to produce autoreactive IgM anti-IgG1 in response to secondary immunization with a number of protein antigens. No anti-IgG1 was produced after a single such immunization, indicating that antigen: IgG1 antibody complexes were responsible for inducing the autoreactive response. The size of the anti-IgG1 response was in some cases massive and of the same order of magnitude as the response to the foreign immunizing material. No significant anti-IgG2a, anti-IgG2b, or anti-IgG3 response was found in mice producing anti-IgG1. Virtually all of the anti-IgG1 material produced was of the IgM class and bound to the Fc region of autologous IgG1. A component of the anti-IgG1 was shown to be able to distinguish between the two mouse IgG1 allotypes. These results suggest that self-reactive anti-IgG is a common component of the secondary immune response of mice that may have powerful physiological and immunoregulatory effects.

scholarly journals Induction of Protective Antiplague Immune Responses by Self-Adjuvanting Bionanoparticles Derived from Engineered Yersinia pestis

2020 ◽  
Vol 88 (5) ◽  
Author(s):  
Xiuran Wang ◽  
Amit K. Singh ◽  
Xiangmin Zhang ◽  
Wei Sun
Keyword(s):  
Immune Responses ◽  
Yersinia Pestis ◽  
Rational Design ◽  
Lipid A ◽  
Vaccine Development ◽  
Lethal Dose ◽  
Outer Membrane Vesicles ◽  
Vector System ◽  
Content Type ◽  
Monophosphoryl Lipid A

ABSTRACT A Yersinia pestis mutant synthesizing an adjuvant form of lipid A (monophosphoryl lipid A, MPLA) displayed increased biogenesis of bacterial outer membrane vesicles (OMVs). To enhance the immunogenicity of the OMVs, we constructed an Asd-based balanced-lethal host-vector system that oversynthesized the LcrV antigen of Y. pestis, raised the amounts of LcrV enclosed in OMVs by the type II secretion system, and eliminated harmful factors like plasminogen activator (Pla) and murine toxin from the OMVs. Vaccination with OMVs containing MPLA and increased amounts of LcrV with diminished toxicity afforded complete protection in mice against subcutaneous challenge with 8 × 105 CFU (80,000 50% lethal dose [LD50]) and intranasal challenge with 5 × 103 CFU (50 LD50) of virulent Y. pestis. This protection was significantly superior to that resulting from vaccination with LcrV/alhydrogel or rF1-V/alhydrogel. At week 4 postimmunization, the OMV-immunized mice showed more robust titers of antibodies against LcrV, Y. pestis whole-cell lysate (YPL), and F1 antigen and more balanced IgG1:IgG2a/IgG2b-derived Th1 and Th2 responses than LcrV-immunized mice. Moreover, potent adaptive and innate immune responses were stimulated in the OMV-immunized mice. Our findings demonstrate that self-adjuvanting Y. pestis OMVs provide a novel plague vaccine candidate and that the rational design of OMVs could serve as a robust approach for vaccine development.

Induction of immune response against a short synthetic peptide antigen coupled to small neutral liposomes containing monophosphoryl lipid a

1993 ◽  
Vol 30 (6) ◽  
pp. 539-547 ◽  
Author(s):  
Martin Friede ◽  
Sylviane Muller ◽  
Jean-Paul Briand ◽  
Marc H.V. Van Regenmortel ◽  
Francis Schuber
Keyword(s):  
Immune Response ◽  
Synthetic Peptide ◽  
Lipid A ◽  
Peptide Antigen ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid

scholarly journals Effect of Different Adjuvants on the Longevity and Strength of Humoral and Cellular Immune Responses to the HCV Envelope Glycoproteins

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 204 ◽  
Author(s):  
Bassel Akache ◽  
Lise Deschatelets ◽  
Blair A. Harrison ◽  
Renu Dudani ◽  
Felicity C. Stark ◽  
...  
Keyword(s):  
T Cells ◽  
Neutralizing Antibodies ◽  
Lipid A ◽  
Cellular Responses ◽  
Current Treatment ◽  
Water Emulsion ◽  
Treatment Regimens ◽  
Immune Parameters ◽  
Monophosphoryl Lipid A ◽  
Oil In Water Emulsion

Infection by Hepatitis C virus (HCV) can lead to liver cirrhosis/hepatocellular carcinoma and remains a major cause of serious disease morbidity and mortality worldwide. However, current treatment regimens remain inaccessible to most patients, particularly in developing countries, and, therefore, the development of a novel vaccine capable of protecting subjects from chronic infection by HCV could greatly reduce the rates of HCV infection, subsequent liver pathogenesis, and in some cases death. Herein, we evaluated two different semi-synthetic archaeosome formulations as an adjuvant to the E1/E2 HCV envelope protein in a murine model and compared antigen-specific humoral (levels of anti-E1/E2 IgG and HCV pseudoparticle neutralization) and cellular responses (numbers of antigen-specific cytokine-producing T cells) to those generated with adjuvant formulations composed of mimetics of commercial adjuvants including a squalene oil-in-water emulsion, aluminum hydroxide/monophosphoryl lipid A (MPLA) and liposome/MPLA/QS-21. In addition, we measured the longevity of these responses, tracking humoral, and cellular responses up to 6 months following vaccination. Overall, we show that the strength and longevity of anti-HCV responses can be influenced by adjuvant selection. In particular, a simple admixed sulfated S-lactosylarchaeol (SLA) archaeosome formulation generated strong levels of HCV neutralizing antibodies and polyfunctional antigen-specific CD4 T cells producing multiple cytokines such as IFN-γ, TNF-α, and IL-2. While liposome/MPLA/QS-21 as adjuvant generated superior cellular responses, the SLA E1/E2 admixed formulation was superior or equivalent to the other tested formulations in all immune parameters tested.

scholarly journals A Potent Adjuvant Monophosphoryl Lipid A Triggers Various Immune Responses, but Not Secretion of IL-1β or Activation of Caspase-1

2006 ◽  
Vol 176 (2) ◽  
pp. 1203-1208 ◽  
Author(s):  
Kazuo Okemoto ◽  
Kiyoshi Kawasaki ◽  
Kentaro Hanada ◽  
Masami Miura ◽  
Masahiro Nishijima
Keyword(s):  
Immune Responses ◽  
Lipid A ◽  
Caspase 1 ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid
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