scholarly journals Adjuvant Activity of Monophosphoryl Lipid A for Nasal and Oral Immunization with Soluble or Liposome-Associated Antigen

2000 ◽  
Vol 68 (10) ◽  
pp. 5509-5516 ◽  
Author(s):  
Noel K. Childers ◽  
Keri L. Miller ◽  
Giang Tong ◽  
Juan Carlos Llarena ◽  
Terrance Greenway ◽  
...  
Keyword(s):  
Lipid A ◽  
Immunoglobulin A ◽  
Oral Immunization ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antibody Activity ◽  
Soluble Antigen ◽  
Adjuvant Activity ◽  
Anamnestic Response ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid

ABSTRACT The effectiveness of monophosphoryl lipid A (MPL) as a mucosal adjuvant was investigated following oral or intranasal (i.n.) administration of an aqueous adjuvant formulation of MPL (MPL-AF) added to soluble antigen or liposomal antigen or incorporated into liposomal antigen membranes. Groups of BALB/c female mice were immunized with 50 to 100 μg of free or liposomal Streptococcus mutans crude glucosyltransferase (C-GTF) with or without MPL-AF added to the vaccine or incorporated into the liposomal membrane. Plasma, saliva, vaginal wash, and fecal extract samples were collected biweekly following immunization and assessed for antigen-specific antibody activity by enzyme-linked immunosorbent assay (ELISA). Mice immunized by the i.n. route had higher levels of salivary, plasma, and vaginal immunoglobulin A (IgA) anti-C-GTF responses and higher levels of plasma IgG anti-C-GTF than the orally immunized groups. A second administration of the vaccine 14 weeks after the initial immunization resulted in an anamnestic response to C-GTF resulting in 10- and 100-fold increases in saliva and plasma IgA and plasma IgG, respectively (in the i.n. immunized groups). Mice receiving a second i.n. immunization with liposomal antigen and MPL-AF had higher salivary IgA anti-C-GTF responses than mice immunized with antigen plus MPL-AF or liposomal antigen (P < 0.05). Plasma IgG anti-C-GTF activity was highest in mice immunized by the i.n. route with antigen formulations containing MPL-AF (P < 0.05). These results demonstrate the effectiveness of MPL-AF as an adjuvant for potentiating mucosal and systemic immune responses to liposomal C-GTF following i.n. immunization.

scholarly journals Mechanisms of Monophosphoryl Lipid A Augmentation of Host Responses to Recombinant HagB from Porphyromonas gingivalis

2002 ◽  
Vol 70 (7) ◽  
pp. 3557-3565 ◽  
Author(s):  
Qiu-Bo Yang ◽  
Michael Martin ◽  
Suzanne M. Michalek ◽  
Jannet Katz
Keyword(s):  
Porphyromonas Gingivalis ◽  
Lipid A ◽  
Costimulatory Molecules ◽  
Th2 Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antibody Activity ◽  
Salivary Iga ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Control Serum

ABSTRACT Porphyromonas gingivalis, a gram-negative, black-pigmented anaerobe, is among the microorganisms implicated in the etiology of adult periodontal disease. This bacterium possesses a number of factors, including hemagglutinins, of potential importance in virulence. Our laboratory has shown the induction of protection to P. gingivalis infection after subcutaneous immunization with recombinant hemagglutinin B (rHagB). The purpose of this study was to determine if humoral antibody responses are induced after intranasal (i.n.) immunization of rHagB and if monophosphoryl lipid A (MPL), a nontoxic derivative of the lipid A region of lipopolysaccharide, acts as a mucosal adjuvant and potentiates responses to rHagB. Further, the effects of MPL on the nature of the response to HagB and on the costimulatory molecules B7-1 and B7-2 on different antigen-presenting cells (APC) were evaluated. Groups of BALB/c mice were immunized three times (2-week intervals) by the i.n. route with HagB (20 μg) alone or with MPL (25 μg). A group of nonimmunized mice served as control. Serum and saliva samples were collected prior to immunization and at approximately 2-week intervals and evaluated for serum immunoglobulin G (IgG) and IgG subclass and for salivary IgA antibody activity by enzyme-linked immunosorbent assay. Mice immunized with rHagB plus MPL had significantly higher salivary IgA (P < 0.05) and serum IgG (P < 0.05) anti-HagB responses than mice immunized with rHagB alone. The IgG1 and IgG2a subclass responses seen in mice immunized with rHagB plus MPL were significantly higher (P < 0.05) than those seen in mice immunized with rHagB only. Further, the IgG2a/IgG1 ratio in the latter group was ≈1, whereas in mice immunized with rHagB plus MPL the ratio was <1. These results provide evidence for the participation of T helper (Th) 1 and Th2 cells in responses to rHagB and that MPL potentiates a type 2 response to HagB. MPL was also shown to preferentially up-regulate B7-2 expression on B cells, whereas a preferential increase in B7-1 costimulatory molecule was seen on macrophages and dendritic cells. These results provide evidence that MPL exerts a differential regulation in the expression of costimulatory molecules on APC.

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 STAT4 is required for the generation of Th1 and Th2, but not Th17 immune responses during monophosphoryl lipid A adjuvant activity

2018 ◽  
Vol 30 (8) ◽  
pp. 385-385
Author(s):  
Sanjay Varikuti ◽  
Steve Oghumu ◽  
Gayathri Natarajan ◽  
Jennifer Kimble ◽  
Rachel H Sperling ◽  
...  
Keyword(s):  
Immune Responses ◽  
Lipid A ◽  
Adjuvant Activity ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Th1 And Th2

scholarly journals STAT4 is required for the generation of Th1 and Th2, but not Th17 immune responses during monophosphoryl lipid A adjuvant activity

2016 ◽  
Vol 28 (11) ◽  
pp. 565-570 ◽  
Author(s):  
Sanjay Varikuti ◽  
Steve Oghumu ◽  
Gayathri Natarajan ◽  
Jennifer Kimble ◽  
Rachel H. Sperling ◽  
...  
Keyword(s):  
Immune Responses ◽  
Lipid A ◽  
Adjuvant Activity ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Th1 And Th2

scholarly journals Immunization with the Haemophilus ducreyi Hemoglobin Receptor HgbA with Adjuvant Monophosphoryl Lipid A Protects Swine from a Homologous but Not a Heterologous Challenge

2010 ◽  
Vol 78 (9) ◽  
pp. 3763-3772 ◽  
Author(s):  
William G. Fusco ◽  
Galyna Afonina ◽  
Igor Nepluev ◽  
Deborah M. Cholon ◽  
Neelima Choudhary ◽  
...  
Keyword(s):  
Lipid A ◽  
Haemophilus Ducreyi ◽  
Class I ◽  
Enzyme Linked Immunosorbent Assay ◽  
Whole Cells ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Heterologous Challenge ◽  
Hemoglobin Binding ◽  
Strict Requirement

ABSTRACTHaemophilus ducreyi, the etiological agent of chancroid, has a strict requirement for heme, which it acquires from its only natural host, humans. Previously, we showed that a vaccine preparation containing the native hemoglobin receptor HgbA purified fromH. ducreyiclass I strain 35000HP (nHgbAI) and administered with Freund's adjuvant provided complete protection against a homologous challenge. In the current study, we investigated whether nHgbAIdispensed with monophosphoryl lipid A (MPL), an adjuvant approved for use in humans, offered protection against a challenge withH. ducreyistrain 35000HP expressing either class I or class II HgbA (35000HPhgbAIand 35000HPhgbAII, respectively). Pigs immunized with the nHgbAI/MPL vaccine were protected against a challenge from homologousH. ducreyistrain 35000HPhgbAIbut not heterologous strain 35000HPhgbAII, as evidenced by the isolation of only strain 35000HPhgbAIIfrom nHgbAI-immunized pigs. Furthermore, histological analysis of the lesions showed striking differences between mock-immunized and nHgbAI-immunized animals challenged with strains 35000HPhgbAIbut not those challenged with strain 35000HPhgbAII. Mock-immunized pigs were not protected from a challenge by either strain. The enzyme-linked immunosorbent assay (ELISA) activity of the nHgbAI/MPL antiserum was lower than the activity of antiserum from animals immunized with the nHgbAI/Freund's vaccine; however, anti-nHgbAIfrom both studies bound whole cells of 35000HPhgbAIbetter than 35000HPhgbAIIand partially blocked hemoglobin binding to nHgbAI. In conclusion, despite eliciting lower antibody ELISA activity than the nHgbAI/Freund's, the nHgbAI/MPL vaccine provided protection against a challenge with homologous but not heterologousH. ducreyi, suggesting that a bivalent HgbA vaccine may be needed.

scholarly journals Potent Adjuvant Activity of Cationic Liposome-DNA Complexes for Genital Herpes Vaccines

2009 ◽  
Vol 16 (5) ◽  
pp. 699-705 ◽  
Author(s):  
David I. Bernstein ◽  
Rhonda D. Cardin ◽  
Fernando J. Bravo ◽  
Jane E. Strasser ◽  
Nicholas Farley ◽  
...  
Keyword(s):  
Genital Herpes ◽  
Lipid A ◽  
Cationic Liposome ◽  
Antibody Responses ◽  
Dna Complexes ◽  
Adjuvant Activity ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Simplex Virus

ABSTRACT Development of a herpes simplex virus (HSV) vaccine is a priority because these infections are common. It appears that potent adjuvants will be required to augment the immune response to subunit HSV vaccines. Therefore, we evaluated cationic liposome-DNA complexes (CLDC) as an adjuvant in a mouse model of genital herpes. Using a whole-virus vaccine (HVAC), we showed that the addition of CLDC improved antibody responses compared to vaccine alone. Most important, CLDC increased survival, reduced symptoms, and decreased vaginal virus replication compared to vaccine alone or vaccine administered with monophosphoryl lipid A (MPL) plus trehalose dicorynomycolate (TDM) following intravaginal challenge of mice. When CLDC was added to an HSV gD2 vaccine, it increased the amount of gamma interferon that was produced from splenocytes stimulated with gD2 compared to the amount produced with gD2 alone or with MPL-alum. The addition of CLDC to the gD2 vaccine also improved the outcome following vaginal HSV type 2 challenge compared to vaccine alone and was equivalent to vaccination with an MPL-alum adjuvant. CLDC appears to be a potent adjuvant for HSV vaccines and should be evaluated further.

Monophosphoryl lipid A analogues with varying 3-O-substitution: synthesis and potent adjuvant activity

2007 ◽  
Vol 342 (6) ◽  
pp. 784-796 ◽  
Author(s):  
Zi-Hua Jiang ◽  
Wladyslaw A. Budzynski ◽  
Dongxu Qiu ◽  
Damayanthi Yalamati ◽  
R. Rao Koganty
Keyword(s):  
Lipid A ◽  
Adjuvant Activity ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid

scholarly journals Role of Innate Immune Factors in the Adjuvant Activity of Monophosphoryl Lipid A

2003 ◽  
Vol 71 (5) ◽  
pp. 2498-2507 ◽  
Author(s):  
Michael Martin ◽  
Suzanne M. Michalek ◽  
Jannet Katz
Keyword(s):  
Map Kinases ◽  
Cell Activation ◽  
Lipid A ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Human Monocytes ◽  
Adjuvant Activity ◽  
Peripheral Blood Mononuclear ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid

ABSTRACT Monophosphoryl lipid A (MPL) is a nontoxic derivative of lipopolysaccharide (LPS) that exhibits adjuvant properties similar to those of the parent LPS molecule. However, the mechanism by which MPL initiates its immunostimulatory properties remains unclear. Due to the involvement of Toll-like receptors in recognizing and transducing intracellular signals in response to LPS, the aim of the present study was to determine the ability of MPL to utilize the Toll-like receptor 2 (TLR2) and TLR4. We provide evidence that MPL differentially utilizes TLR2 and TLR4 for the induction of tumor necrosis factor alpha, interleukin 10 (IL-10), and IL-12 by purified human monocytes as well as by human peripheral blood mononuclear cells. Assessment of NF-κB activity demonstrated that MPL utilized TLR2 and especially TLR4 for the activation of NF-κB p65 by human monocytes. In addition, stimulation of human monocytes by MPL led to an up-regulation of the costimulatory molecules CD80 and CD86, an effect that could be reduced by pretreatment of cells with a monoclonal antibody to TLR2 or TLR4. Analysis of MPL-induced activation of the extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinases revealed that MPL utilized both TLR2 and TLR4 for the phosphorylation of ERK1/2, while TLR4 was the predominant receptor involved in the ability of MPL to phosphorylate p38. Moreover, using selective inhibitors for MAP kinase kinase (PD98059) and p38 (SB203580), we show that ERK1/2 exhibited differential effects on production of TNF-α and IL-12 p40 by human monocytes, whereas MPL-induced activation of p38 appeared to be predominantly involved in production of IL-10 and IL-12 p40 by MPL-stimulated monocytes. Taken together, these findings aid in understanding the cellular mechanisms by which MPL induces host cell activation and subsequent adjuvant properties.

scholarly journals Comparison of Intranasal and Intramuscular Immunization against Human Immunodeficiency Virus Type 1 with a DNA-Monophosphoryl Lipid A Adjuvant Vaccine

1998 ◽  
Vol 66 (2) ◽  
pp. 823-826 ◽  
Author(s):  
Shin Sasaki ◽  
Kenji Hamajima ◽  
Jun Fukushima ◽  
Atsushi Ihata ◽  
Norihisa Ishii ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Lipid A ◽  
Immunoglobulin A ◽  
Cell Mediated Immunity ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Immunodeficiency Virus

ABSTRACT We compared immune responses to intranasal and intramuscular DNA vaccinations against human immunodeficiency virus type 1 with monophosphoryl lipid A (MPL) used as an adjuvant. Both routes of vaccination resulted in similar levels of cell-mediated immunity, but the intestinal secretory immunoglobulin A response was higher following intranasal immunization than after intramuscular immunization. MPL demonstrated its adjuvanticity in vaccination by both routes.

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