Molecular and cellular signatures of human vaccine adjuvants.

Abstract:

:Oil-in-water emulsions are potent human adjuvants used for effective pandemic influenza vaccines; however, their mechanism of action is still unknown. By combining microarray and immunofluorescence analysis, we monitored the effects of the adjuvants MF59 oil-in-water emulsion, CpG, and alum in the mouse muscle. MF59 induced a time-dependent change in the expression of 891 genes, whereas CpG and alum regulated 387 and 312 genes, respectively. All adjuvants modulated a common set of 168 genes and promoted antigen-presenting cell recruitment. MF59 was the stronger inducer of cytokines, cytokine receptors, adhesion molecules involved in leukocyte migration, and antigen-presentation genes. In addition, MF59 triggered a more rapid influx of CD11b+ blood cells compared with other adjuvants. The early biomarkers selected by microarray, JunB and Ptx3, were used to identify skeletal muscle as a direct target of MF59. We propose that oil-in-water emulsions are the most efficient human vaccine adjuvants, because they induce an early and strong immunocompetent environment at the injection site by targeting muscle cells.

authors

Mosca F,Tritto E,Muzzi A,Monaci E,Bagnoli F,Iavarone C,O'Hagan D,Rappuoli R,De Gregorio E

doi

10.1073/pnas.0804699105

subject

Has Abstract

pub_date

2008-07-29 00:00:00

pages

10501-6

issue

30

eissn

0027-8424

issn

1091-6490

pii

0804699105

journal_volume

105

pub_type

杂志文章
  • Pyrolysis of organomercury compounds: investigation by the method of matrix isolation.

    abstract::The method of matrix isolation has been used to investigate mechanisms of gas-phase chemical reactions, in particular the pyrolysis of some organomercury compounds. A molecular beam of pyrolysis products was condensed simultaneously with a large excess of rare gas at temperatures from 5 to 15 degrees K to form a matri...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.68.12.3238

    authors: Maltsev AK,Mikaelian RG,Nefedov OM,Hauge RH,Margrave JL

    更新日期:1971-12-01 00:00:00

  • Generalizing Fisher's "reproductive value": linear differential and difference equations of "dilute" biological systems.

    abstract::R. A. Fisher's 1930 "reproductive value" is defined as the contribution made by a population's initial age elements to its asymptotically dominating exponential growth mode. For the Leslie discrete-time model, it is the characteristic row vector of the Leslie matrix, and for the integral-equation model of Lotka the si...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.74.11.5189

    authors: Samuelson PA

    更新日期:1977-11-01 00:00:00

  • Subcellular distribution of Lck during CD4 T-cell maturation in the thymic medulla regulates the T-cell activation threshold.

    abstract::Mature peripheral T cells respond to foreign but not to self-antigens. During development in the thymus, deletion of high-affinity self-reactive immature thymocytes contributes to tolerance of mature T cells. However, double-positive thymocytes are positively selected to survive if they respond to self-peptide-MHC com...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1119272109

    authors: Stephen TL,Wilson BS,Laufer TM

    更新日期:2012-05-08 00:00:00

  • On the mechanism of recombination hotspot scanning during double-stranded DNA break resection.

    abstract::Double-stranded DNA break repair by homologous recombination is initiated by resection of free DNA ends to produce a 3'-ssDNA overhang. In bacteria, this reaction is catalyzed by helicase-nuclease complexes such as AddAB in a manner regulated by specific recombination hotspot sequences called Crossover hotspot instiga...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1303035110

    authors: Carrasco C,Gilhooly NS,Dillingham MS,Moreno-Herrero F

    更新日期:2013-07-09 00:00:00

  • A model for protein synthesis involving the intermediate formation of peptidyl-5S RNA.

    abstract::A model for protein synthesis is proposed in which the donor for the peptide elongation reaction is peptidyl-5S RNA. Space-filling models show that peptide bond formation between peptidyl-5S RNA and aminoacyl-tRNA is eminently feasible from a stereochemical point of view. The peptide is transferred to 5S RNA, while at...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.68.10.2357

    authors: Raacke ID

    更新日期:1971-10-01 00:00:00

  • Expression of monocarboxylate transporter mRNAs in mouse brain: support for a distinct role of lactate as an energy substrate for the neonatal vs. adult brain.

    abstract::Under particular circumstances like lactation and fasting, the blood-borne monocarboxylates acetoacetate, beta-hydroxybutyrate, and lactate represent significant energy substrates for the brain. Their utilization is dependent on a transport system present on both endothelial cells forming the blood-brain barrier and o...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.7.3990

    authors: Pellerin L,Pellegri G,Martin JL,Magistretti PJ

    更新日期:1998-03-31 00:00:00

  • Insulin receptors in beta-cells are critical for islet compensatory growth response to insulin resistance.

    abstract::Insulin and insulin-like growth factor 1 (IGF1) are ubiquitous growth factors that regulate proliferation in most mammalian tissues including pancreatic islets. To explore the specificity of insulin receptors in compensatory beta-cell growth, we examined two models of insulin resistance. In the first model, we used li...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0608703104

    authors: Okada T,Liew CW,Hu J,Hinault C,Michael MD,Krtzfeldt J,Yin C,Holzenberger M,Stoffel M,Kulkarni RN

    更新日期:2007-05-22 00:00:00

  • Structure of a single-chain antibody variable domain (Fv) fragment complexed with a carbohydrate antigen at 1.7-A resolution.

    abstract::We describe here the 1.7-A resolution structure of a single-chain antibody variable domain (scFv) molecule, based on the carbohydrate-binding antibody Se155-4, complexed with the trisaccharide ligand alpha-D-Gal(1-->2)[alpha-D-Abe(1-->3)]alpha-D-Manp1-->OMe, where Abe is abequose. The scFv expressed in Escherichia col...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.14.6423

    authors: Zdanov A,Li Y,Bundle DR,Deng SJ,MacKenzie CR,Narang SA,Young NM,Cygler M

    更新日期:1994-07-05 00:00:00

  • Climate change is affecting altitudinal migrants and hibernating species.

    abstract::Calendar date of the beginning of the growing season at high altitude in the Colorado Rocky Mountains is variable but has not changed significantly over the past 25 years. This result differs from growing evidence from low altitudes that climate change is resulting in a longer growing season, earlier migrations, and e...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.97.4.1630

    authors: Inouye DW,Barr B,Armitage KB,Inouye BD

    更新日期:2000-02-15 00:00:00

  • Power law tails in phylogenetic systems.

    abstract::Covariance analysis of protein sequence alignments uses coevolving pairs of sequence positions to predict features of protein structure and function. However, current methods ignore the phylogenetic relationships between sequences, potentially corrupting the identification of covarying positions. Here, we use random m...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1711913115

    authors: Qin C,Colwell LJ

    更新日期:2018-01-23 00:00:00

  • Capping protein regulates actin dynamics during cytokinetic midbody maturation.

    abstract::During cytokinesis, a cleavage furrow generated by actomyosin ring contraction is restructured into the midbody, a platform for the assembly of the abscission machinery that controls the final separation of daughter cells. The polymerization state of F-actin is important during assembly, ingression, disassembly, and c...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1722281115

    authors: Terry SJ,Donà F,Osenberg P,Carlton JG,Eggert US

    更新日期:2018-02-27 00:00:00

  • Protein-solvent preferential interactions, protein hydration, and the modulation of biochemical reactions by solvent components.

    abstract::Solvent additives (cosolvents, osmolytes) modulate biochemical reactions if, during the course of the reaction, there is a change in preferential interactions of solvent components with the reacting system. Preferential interactions can be expressed in terms of preferential binding of the cosolvent or its preferential...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.122225399

    authors: Timasheff SN

    更新日期:2002-07-23 00:00:00

  • RNA-protein hybrid ribozymes that efficiently cleave any mRNA independently of the structure of the target RNA.

    abstract::Ribozyme activity in vivo depends on achieving high-level expression, intracellular stability, target colocalization, and cleavage site access. At present, target site selection is problematic because of unforeseeable secondary and tertiary RNA structures that prevent cleavage. To overcome this design obstacle, we wis...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.091411398

    authors: Warashina M,Kuwabara T,Kato Y,Sano M,Taira K

    更新日期:2001-05-08 00:00:00

  • lambda Rap protein is a structure-specific endonuclease involved in phage recombination.

    abstract::Bacteriophage lambda encodes a number of genes involved in the recombinational repair of DNA double-strand breaks. The product of one of these genes, rap, has been purified. Truncated Rap proteins that copurify with the full-length form are derived, at least in part, from a rho-dependent transcription terminator locat...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.23.13507

    authors: Sharples GJ,Corbett LM,Graham IR

    更新日期:1998-11-10 00:00:00

  • Epicardial retinoid X receptor alpha is required for myocardial growth and coronary artery formation.

    abstract::Vitamin A signals play critical roles during embryonic development. In particular, heart morphogenesis depends on vitamin A signals mediated by the retinoid X receptor alpha (RXRalpha), as the systemic mutation of this receptor results in thinning of the myocardium and embryonic lethality. However, the molecular and c...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0504343102

    authors: Merki E,Zamora M,Raya A,Kawakami Y,Wang J,Zhang X,Burch J,Kubalak SW,Kaliman P,Izpisua Belmonte JC,Chien KR,Ruiz-Lozano P

    更新日期:2005-12-20 00:00:00

  • Maximum leaf conductance driven by CO2 effects on stomatal size and density over geologic time.

    abstract::Stomatal pores are microscopic structures on the epidermis of leaves formed by 2 specialized guard cells that control the exchange of water vapor and CO(2) between plants and the atmosphere. Stomatal size (S) and density (D) determine maximum leaf diffusive (stomatal) conductance of CO(2) (g(c(max))) to sites of assim...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0904209106

    authors: Franks PJ,Beerling DJ

    更新日期:2009-06-23 00:00:00

  • Methods for causal inference from gene perturbation experiments and validation.

    abstract::Inferring causal effects from observational and interventional data is a highly desirable but ambitious goal. Many of the computational and statistical methods are plagued by fundamental identifiability issues, instability, and unreliable performance, especially for large-scale systems with many measured variables. We...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1510493113

    authors: Meinshausen N,Hauser A,Mooij JM,Peters J,Versteeg P,Bühlmann P

    更新日期:2016-07-05 00:00:00

  • Chemical ecology: a view from the pharmaceutical industry.

    abstract::Biological diversity reflects an underlying molecular diversity. The molecules found in nature may be regarded as solutions to challenges that have been confronted and overcome during molecular evolution. As our understanding of these solutions deepens, the efficiency with which we can discover and/or design new treat...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,评审

    doi:10.1073/pnas.92.1.75

    authors: Caporale LH

    更新日期:1995-01-03 00:00:00

  • Karyophilic proteins: polypeptides synthesized in vitro accumulate in the nucleus on microinjection into the cytoplasm of amphibian oocytes.

    abstract::The specific nucleocytoplasmic compartmentalization of proteins has been examined for some major soluble acidic nuclear proteins in oocytes of different amphibia. Proteins synthesized and radioactively labeled by translation in vitro, by using mRNA from ovaries of the frog Xenopus laevis, were injected into the cytopl...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.17.5302

    authors: Dabauvalle MC,Franke WW

    更新日期:1982-09-01 00:00:00

  • Isolation and characterization of DNA sequences amplified in multidrug-resistant hamster cells.

    abstract::The mechanism by which mammalian cells acquire resistance to chemotherapeutic agents has been investigated by using molecular genetic techniques. LZ and C5, two independently derived multidrug-resistant Chinese hamster cell lines, share specific amplified DNA sequences. We demonstrate that commonly amplified DNA seque...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.2.337

    authors: Gros P,Croop J,Roninson I,Varshavsky A,Housman DE

    更新日期:1986-01-01 00:00:00

  • Annexin 2-caveolin 1 complex is a target of ezetimibe and regulates intestinal cholesterol transport.

    abstract::Modulation of cholesterol absorption in the intestine, the primary site of dietary cholesterol uptake in humans, can have profound clinical implications. We have undertaken a reverse genetic approach by disrupting putative cholesterol processing genes in zebrafish larvae by using morpholino (MO) antisense oligonucleot...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,收录出版

    doi:10.1073/pnas.0400441101

    authors: Smart EJ,De Rose RA,Farber SA

    更新日期:2004-03-09 00:00:00

  • Pathogenetic mechanisms of amyloid A amyloidosis.

    abstract::Systemic amyloid A (AA) amyloidosis is a serious complication of chronic inflammation. Serum AA protein (SAA), an acute phase plasma protein, is deposited extracellularly as insoluble amyloid fibrils that damage tissue structure and function. Clinical AA amyloidosis is typically preceded by many years of active inflam...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1306621110

    authors: Simons JP,Al-Shawi R,Ellmerich S,Speck I,Aslam S,Hutchinson WL,Mangione PP,Disterer P,Gilbertson JA,Hunt T,Millar DJ,Minogue S,Bodin K,Pepys MB,Hawkins PN

    更新日期:2013-10-01 00:00:00

  • Peptide and nucleotide sequences of rat CD4 (W3/25) antigen: evidence for derivation from a structure with four immunoglobulin-related domains.

    abstract::The rat W3/25 antigen was the first marker antigen of helper T lymphocytes to be identified. Subsequently, the human OKT4 antigen (now called CD4) was described, and cell distribution and functional data suggested that W3/25 and OKT4 antigens were homologous. This is now confirmed by the matching of peptide sequences ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.6.1649

    authors: Clark SJ,Jefferies WA,Barclay AN,Gagnon J,Williams AF

    更新日期:1987-03-01 00:00:00

  • Plasminogen activator secretion by granule neurons in cultures of developing cerebellum.

    abstract::Dispersed cell cultures were established from 7- to 9-day postnatal mouse cerebellum. The fibrin slice method was used to obtain a localization of plasminogen activator production to specific cells. Fibrinolytically active cells were small (5- to 8-micrometer diameter), round, and occurred singly or in aggregates. Fib...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.12.7810

    authors: Krystosek A,Seeds NW

    更新日期:1981-12-01 00:00:00

  • The c-ring stoichiometry of ATP synthase is adapted to cell physiological requirements of alkaliphilic Bacillus pseudofirmus OF4.

    abstract::The c-rings of ATP synthases consist of individual c-subunits, all of which harbor a conserved motif of repetitive glycine residues (GxGxGxG) important for tight transmembrane α-helix packing. The c-ring stoichiometry determines the number of ions transferred during enzyme operation and has a direct impact on the ion-...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1303333110

    authors: Preiss L,Klyszejko AL,Hicks DB,Liu J,Fackelmayer OJ,Yildiz Ö,Krulwich TA,Meier T

    更新日期:2013-05-07 00:00:00

  • Relationship between the soluble glutathione-dependent delta 5-3-ketosteroid isomerase and the glutathione S-transferases of the liver.

    abstract::Soluble, glutathione-stimulated delta 5-3-ketosteroid isomerase (EC 5.3.3.A) activity of human and rat liver resides in very basic proteins with molecular weights of about 45,000 which are present in high concentrations in these tissues. Physiochemical and immunological evidence is presented for the identity of the pr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.74.1.158

    authors: Benson AM,Talalay P,Keen JH,Jakoby WB

    更新日期:1977-01-01 00:00:00

  • Type II protein arginine methyltransferase 5 (PRMT5) is required for circadian period determination in Arabidopsis thaliana.

    abstract::Posttranslational modification is an important element in circadian clock function from cyanobacteria through plants and mammals. For example, a number of key clock components are phosphorylated and thereby marked for subsequent ubiquitination and degradation. Through forward genetic analysis we demonstrate that prote...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1011987107

    authors: Hong S,Song HR,Lutz K,Kerstetter RA,Michael TP,McClung CR

    更新日期:2010-12-07 00:00:00

  • Evolutionary and structural influences on light chain constant (CL) region of human and mouse immunoglobulins.

    abstract::A comparison of five constant region sequences of human and mouse k and lambda immunoglobulin chains has been undertaken in order to reveal sequence homologies and evolutionary relationships. Simultaneously, a comparison with the three-dimensional structure of one mouse k-chain (McPC 603) has suggested structural reas...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.7.2785

    authors: Kabat EA,Padlan EA,Davies DR

    更新日期:1975-07-01 00:00:00

  • Identification of IL-17-producing FOXP3+ regulatory T cells in humans.

    abstract::IL-17-producing CD4(+) T helper (Th17) cells have recently been defined as a unique subset of proinflammatory helper cells whose development depends on signaling initiated by IL-6 and TGF-beta, autocrine activity of IL-21, activation of STAT3, and induction of the orphan nuclear receptor RORgammat. The maintenance, ex...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0900408106

    authors: Voo KS,Wang YH,Santori FR,Boggiano C,Wang YH,Arima K,Bover L,Hanabuchi S,Khalili J,Marinova E,Zheng B,Littman DR,Liu YJ

    更新日期:2009-03-24 00:00:00

  • DYNC1H1 mutations associated with neurological diseases compromise processivity of dynein-dynactin-cargo adaptor complexes.

    abstract::Mutations in the human DYNC1H1 gene are associated with neurological diseases. DYNC1H1 encodes the heavy chain of cytoplasmic dynein-1, a 1.4-MDa motor complex that traffics organelles, vesicles, and macromolecules toward microtubule minus ends. The effects of the DYNC1H1 mutations on dynein motility, and consequently...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1620141114

    authors: Hoang HT,Schlager MA,Carter AP,Bullock SL

    更新日期:2017-02-28 00:00:00