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 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 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.

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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