Antibody-based protection against HIV infection by vectored immunoprophylaxis.

Abstract:

:Despite tremendous efforts, development of an effective vaccine against human immunodeficiency virus (HIV) has proved an elusive goal. Recently, however, numerous antibodies have been identified that are capable of neutralizing most circulating HIV strains. These antibodies all exhibit an unusually high level of somatic mutation, presumably owing to extensive affinity maturation over the course of continuous exposure to an evolving antigen. Although substantial effort has focused on the design of immunogens capable of eliciting antibodies de novo that would target similar epitopes, it remains uncertain whether a conventional vaccine will be able to elicit analogues of the existing broadly neutralizing antibodies. As an alternative to immunization, vector-mediated gene transfer could be used to engineer secretion of the existing broadly neutralizing antibodies into the circulation. Here we describe a practical implementation of this approach, which we call vectored immunoprophylaxis (VIP), which in mice induces lifelong expression of these monoclonal antibodies at high concentrations from a single intramuscular injection. This is achieved using a specialized adeno-associated virus vector optimized for the production of full-length antibody from muscle tissue. We show that humanized mice receiving VIP appear to be fully protected from HIV infection, even when challenged intravenously with very high doses of replication-competent virus. Our results suggest that successful translation of this approach to humans may produce effective prophylaxis against HIV.

journal_name

Nature

journal_title

Nature

authors

Balazs AB,Chen J,Hong CM,Rao DS,Yang L,Baltimore D

doi

10.1038/nature10660

subject

Has Abstract

pub_date

2011-11-30 00:00:00

pages

81-4

issue

7379

eissn

0028-0836

issn

1476-4687

pii

nature10660

journal_volume

481

pub_type

杂志文章

相关文献

NATURE文献大全
  • Magnetic phase control by an electric field.

    abstract::The quest for higher data density in information storage is motivating investigations into approaches for manipulating magnetization by means other than magnetic fields. This is evidenced by the recent boom in magnetoelectronics and 'spintronics', where phenomena such as carrier effects in magnetic semiconductors and ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature02728

    authors: Lottermoser T,Lonkai T,Amann U,Hohlwein D,Ihringer J,Fiebig M

    更新日期:2004-07-29 00:00:00

  • Late Tharsis formation and implications for early Mars.

    abstract::The Tharsis region is the largest volcanic complex on Mars and in the Solar System. Young lava flows cover its surface (from the Amazonian period, less than 3 billion years ago) but its growth started during the Noachian era (more than 3.7 billion years ago). Its position has induced a reorientation of the planet with...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature17171

    authors: Bouley S,Baratoux D,Matsuyama I,Forget F,Séjourné A,Turbet M,Costard F

    更新日期:2016-03-17 00:00:00

  • Suppressor effects and cyclic AMP accumulation by the CD29 molecule of CD4+ lymphocytes.

    abstract::Integrins are a superfamily of related molecules whose function, where known, is to mediate adhesion. The so-called very-late-activation antigen (VLA) family includes at least five distinct heterodimers, each composed of a unique alpha-subunit non-covalently associated with a common beta-subunit. Several members of th...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/339152a0

    authors: Groux H,Huet S,Valentin H,Pham D,Bernard A

    更新日期:1989-05-11 00:00:00

  • Modulation of glycine receptor chloride channels by cAMP-dependent protein kinase in spinal trigeminal neurons.

    abstract::Glycine is an important inhibitory transmitter in the brainstem and spinal cord. In the trigeminal subnucleus caudalis (medullary dorsal horn) and in the spinal dorsal horn (the relaying centres for processing pain and sensory information), glycine inhibits the glutamate-evoked depolarization and depresses firing of n...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/348242a0

    authors: Song YM,Huang LY

    更新日期:1990-11-15 00:00:00

  • Cholinergic neurones acquire adrenergic neurotransmitters when transplanted into an embryo.

    abstract::During development, cells become progressively restricted, until they reach their final phenotype. Differentiation was originally thought to be irreversible, but phenotypic plasticity has been observed in a variety of cell types, for example sympathetic neurones, the limb blastema and some glial cell types. A detailed...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/324569a0

    authors: Coulombe JN,Bronner-Fraser M

    更新日期:1986-12-11 00:00:00

  • A candidate NAD+ transporter in an intracellular bacterial symbiont related to Chlamydiae.

    abstract::Bacteria living within eukaryotic cells can be essential for the survival or reproduction of the host but in other cases are among the most successful pathogens. Environmental Chlamydiae, including strain UWE25, thrive as obligate intracellular symbionts within protozoa; are recently discovered relatives of major bact...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature03131

    authors: Haferkamp I,Schmitz-Esser S,Linka N,Urbany C,Collingro A,Wagner M,Horn M,Neuhaus HE

    更新日期:2004-12-02 00:00:00

  • Evolutionary instability of ectomycorrhizal symbioses in basidiomycetes.

    abstract::Mycorrhizae, the symbiotic associations of plant roots and fungal hyphae, are classic examples of mutualisms. In these ecologically important associations, the fungi derive photosynthetic sugars from their plant hosts, which in turn benefit from fungus-mediated uptake of mineral nutrients. Early views on the evolution...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/35035065

    authors: Hibbett DS,Gilbert LB,Donoghue MJ

    更新日期:2000-09-28 00:00:00

  • A mechanism for the suppression of homologous recombination in G1 cells.

    abstract::DNA repair by homologous recombination is highly suppressed in G1 cells to ensure that mitotic recombination occurs solely between sister chromatids. Although many homologous recombination factors are cell-cycle regulated, the identity of the events that are both necessary and sufficient to suppress recombination in G...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature16142

    authors: Orthwein A,Noordermeer SM,Wilson MD,Landry S,Enchev RI,Sherker A,Munro M,Pinder J,Salsman J,Dellaire G,Xia B,Peter M,Durocher D

    更新日期:2015-12-17 00:00:00

  • Violation of the incompressibility of liquid by simple shear flow.

    abstract::In standard fluid dynamics, the density change associated with flow is often assumed to be negligible, implying that the fluid is incompressible. For example, this has been established for simple shear flows, where no pressure change is associated with flow: there is no volume deformation due to viscous stress and ine...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature05119

    authors: Furukawa A,Tanaka H

    更新日期:2006-09-28 00:00:00

  • Intracellular calcium dependence of transmitter release rates at a fast central synapse.

    abstract::Calcium-triggered fusion of synaptic vesicles and neurotransmitter release are fundamental signalling steps in the central nervous system. It is generally assumed that fast transmitter release is triggered by elevations in intracellular calcium concentration ([Ca2+]i) to at least 100 microM near the sites of vesicle f...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/35022702

    authors: Schneggenburger R,Neher E

    更新日期:2000-08-24 00:00:00

  • Control of somatic tissue differentiation by the long non-coding RNA TINCR.

    abstract::Several of the thousands of human long non-coding RNAs (lncRNAs) have been functionally characterized; however, potential roles for lncRNAs in somatic tissue differentiation remain poorly understood. Here we show that a 3.7-kilobase lncRNA, terminal differentiation-induced ncRNA (TINCR), controls human epidermal diffe...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature11661

    authors: Kretz M,Siprashvili Z,Chu C,Webster DE,Zehnder A,Qu K,Lee CS,Flockhart RJ,Groff AF,Chow J,Johnston D,Kim GE,Spitale RC,Flynn RA,Zheng GX,Aiyer S,Raj A,Rinn JL,Chang HY,Khavari PA

    更新日期:2013-01-10 00:00:00

  • The codon CUG is read as serine in an asporogenic yeast Candida cylindracea.

    abstract::Deviations from the universal genetic code have been reported for several microorganisms. Termination codons are used for coding some amino acids in Paramecium, Mycoplasma or Tetrahymena, and in Escherichia coli, the UGA termination codon is used to code for selenocysteine. In mitochondria, the changes of sense codons...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/341164a0

    authors: Kawaguchi Y,Honda H,Taniguchi-Morimura J,Iwasaki S

    更新日期:1989-09-14 00:00:00

  • Endothelins are vascular-derived axonal guidance cues for developing sympathetic neurons.

    abstract::During development, sympathetic neurons extend axons along a myriad of distinct trajectories, often consisting of arteries, to innervate one of a large variety of distinct final target tissues. Whether or not subsets of neurons within complex sympathetic ganglia are predetermined to innervate select end-organs is unkn...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature06859

    authors: Makita T,Sucov HM,Gariepy CE,Yanagisawa M,Ginty DD

    更新日期:2008-04-10 00:00:00

  • Ion sieving in graphene oxide membranes via cationic control of interlayer spacing.

    abstract::Graphene oxide membranes-partially oxidized, stacked sheets of graphene-can provide ultrathin, high-flux and energy-efficient membranes for precise ionic and molecular sieving in aqueous solution. These materials have shown potential in a variety of applications, including water desalination and purification, gas and ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature24044

    authors: Chen L,Shi G,Shen J,Peng B,Zhang B,Wang Y,Bian F,Wang J,Li D,Qian Z,Xu G,Liu G,Zeng J,Zhang L,Yang Y,Zhou G,Wu M,Jin W,Li J,Fang H

    更新日期:2017-10-19 00:00:00

  • Regionally restricted developmental defects resulting from targeted disruption of the mouse homeobox gene hox-1.5.

    abstract::Gene targeting in mouse embryo-derived stem cells has been used to disrupt the homeobox gene hox-1.5. Mice heterozygous at the hox-1.5 locus appear normal, whereas hox-1.5-/hox-1.5- mice die at or shortly after birth. These homozygotes are athymic, aparathyroid, have reduced thyroid and submaxillary tissue and exhibit...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/350473a0

    authors: Chisaka O,Capecchi MR

    更新日期:1991-04-11 00:00:00

  • Noise-induced enhancement of signal transduction across voltage-dependent ion channels.

    abstract::The presence of noise in a signal transduction system usually interferes with its ability to transfer information reliably. But many nonlinear systems can use noise to enhance performance, and this phenomenon, called stochastic resonance, may underlie the extraordinary ability of some biological systems to detect and ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/378362a0

    authors: Bezrukov SM,Vodyanoy I

    更新日期:1995-11-23 00:00:00

  • Sequence of simian immunodeficiency virus and its relationship to the human immunodeficiency viruses.

    abstract::The characterization of HIV-1 (HTLV-III/LAV), the human retrovirus associated with AIDS (acquired immune deficiency syndrome) has led to the identification of a group of related human and simian retroviruses which also infect CD4-bearing T lymphocytes. Simian T-lymphotropic virus type III (simian immodeficiency virus)...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/328539a0

    authors: Franchini G,Gurgo C,Guo HG,Gallo RC,Collalti E,Fargnoli KA,Hall LF,Wong-Staal F,Reitz MS Jr

    更新日期:1987-08-06 00:00:00

  • Author Correction: The wide-binary origin of (2014) MU69-like Kuiper belt contact binaries.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Nature

    pub_type: 已发布勘误

    doi:10.1038/s41586-020-2351-4

    authors: Grishin E,Malamud U,Perets HB,Wandel O,Schäfer CM

    更新日期:2020-06-01 00:00:00

  • An alternative approach to establishing trade-offs among greenhouse gases.

    abstract::The Kyoto Protocol permits countries to meet part of their emission reduction obligations by cutting back on gases other than CO2 (ref. 1). This approach requires a definition of trade-offs among the radiatively active gases. The Intergovernmental Panel on Climate Change has suggested global warming potentials for thi...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/35070541

    authors: Manne AS,Richels RG

    更新日期:2001-04-05 00:00:00

  • Structure of a human common cold virus and functional relationship to other picornaviruses.

    abstract::We report the first atomic resolution structure of an animal virus, human rhinovirus 14. It is strikingly similar to known icosahedral plant RNA viruses. Four neutralizing immunogenic regions have been identified. These, and corresponding antigenic sequences of polio and foot-and-mouth disease viruses, reside on exter...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/317145a0

    authors: Rossmann MG,Arnold E,Erickson JW,Frankenberger EA,Griffith JP,Hecht HJ,Johnson JE,Kamer G,Luo M,Mosser AG

    更新日期:1985-09-12 00:00:00

  • Encoding of danger by parabrachial CGRP neurons.

    abstract::Animals must respond to various threats to survive. Neurons that express calcitonin gene-related peptide in the parabrachial nucleus (CGRPPBN neurons) relay sensory signals that contribute to satiation and pain-induced fear behaviour, but it is unclear how they encode these distinct processes. Here, by recording calci...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature25511

    authors: Campos CA,Bowen AJ,Roman CW,Palmiter RD

    更新日期:2018-03-29 00:00:00

  • Identification and characterization of a bacterial hydrosulphide ion channel.

    abstract::The hydrosulphide ion (HS(-)) and its undissociated form, hydrogen sulphide (H(2)S), which are believed to have been critical to the origin of life on Earth, remain important in physiology and cellular signalling. As a major metabolite in anaerobic bacterial growth, hydrogen sulphide is a product of both assimilatory ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature10881

    authors: Czyzewski BK,Wang DN

    更新日期:2012-03-11 00:00:00

  • Heterogeneous integration of single-crystalline complex-oxide membranes.

    abstract::Complex-oxide materials exhibit a vast range of functional properties desirable for next-generation electronic, spintronic, magnetoelectric, neuromorphic, and energy conversion storage devices1-4. Their physical functionalities can be coupled by stacking layers of such materials to create heterostructures and can be f...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/s41586-020-1939-z

    authors: Kum HS,Lee H,Kim S,Lindemann S,Kong W,Qiao K,Chen P,Irwin J,Lee JH,Xie S,Subramanian S,Shim J,Bae SH,Choi C,Ranno L,Seo S,Lee S,Bauer J,Li H,Lee K,Robinson JA,Ross CA,Schlom DG,Rzchowski MS,Eom CB,Kim J

    更新日期:2020-02-01 00:00:00

  • Thermolysis of fluoropolymers as a potential source of halogenated organic acids in the environment.

    abstract::Following the introduction of hydrochlorofluorocarbon (HCFCs) and hydrofluorocarbon (HFCs) gases as replacements for the ozone-destroying chlorofluorocarbons (CFCs), it has been discovered that HCFCs/HFCs can degrade in the atmosphere to produce trifluoroacetic acid, a compound with no known loss mechanisms in the env...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/35085548

    authors: Ellis DA,Mabury SA,Martin JW,Muir DC

    更新日期:2001-07-19 00:00:00

  • Ultrafast terahertz probes of transient conducting and insulating phases in an electron-hole gas.

    abstract::Many-body systems in nature exhibit complexity and self-organization arising from seemingly simple laws. For example, the long-range Coulomb interaction between electrical charges has a simple form, yet is responsible for a plethora of bound states in matter, ranging from the hydrogen atom to complex biochemical struc...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature01676

    authors: Kaindl RA,Carnahan MA,Hägele D,Lövenich R,Chemla DS

    更新日期:2003-06-12 00:00:00

  • Visualization of ordered genomic RNA and localization of transcriptional complexes in rotavirus.

    abstract::In double-stranded-RNA (dsRNA) viruses found in animals, bacteria and yeast, the genome is transcribed within the structurally intact core of the virion with extraordinary efficiency. The structural organization of the genome and the enzymes involved in the transcription inside any of these viruses, critical for under...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/382471a0

    authors: Prasad BV,Rothnagel R,Zeng CQ,Jakana J,Lawton JA,Chiu W,Estes MK

    更新日期:1996-08-01 00:00:00

  • Evolution of ageing.

    abstract::An evolutionary view of ageing suggests that mortality may be due to an energy-saving strategy of reduced error regulation in somatic cells. This supports Orgel's 'error catastrophe' hypothesis and offers a new basis for the study of normal and abnormal ageing syndromes and of apparently immortal transformed cell line...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/270301a0

    authors: Kirkwood TB

    更新日期:1977-11-24 00:00:00

  • Nitric oxide functions as a signal in plant disease resistance.

    abstract::Recognition of an avirulent pathogen triggers the rapid production of the reactive oxygen intermediates superoxide (O2-) and hydrogen peroxide (H2O2). This oxidative burst drives crosslinking of the cell wall, induces several plant genes involved in cellular protection and defence, and is necessary for the initiation ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/29087

    authors: Delledonne M,Xia Y,Dixon RA,Lamb C

    更新日期:1998-08-06 00:00:00

  • Human herpesvirus KSHV encodes a constitutively active G-protein-coupled receptor linked to cell proliferation.

    abstract::Kaposi's sarcoma-associated herpesvirus (KSHV, also known as human herpesvirus 8, or HHV 8) is a virus that is consistently present in Kaposi's sarcoma and in primary-effusion (body-cavity-based) lymphomas, malignancies that occur frequently, but not exclusively, in AIDS patients. KSHV is a gamma herpesvirus with homo...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/385347a0

    authors: Arvanitakis L,Geras-Raaka E,Varma A,Gershengorn MC,Cesarman E

    更新日期:1997-01-23 00:00:00

  • Horsetails and ferns are a monophyletic group and the closest living relatives to seed plants.

    abstract::Most of the 470-million-year history of plants on land belongs to bryophytes, pteridophytes and gymnosperms, which eventually yielded to the ecological dominance by angiosperms 90 Myr ago. Our knowledge of angiosperm phylogeny, particularly the branching order of the earliest lineages, has recently been increased by t...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/35054555

    authors: Pryer KM,Schneider H,Smith AR,Cranfill R,Wolf PG,Hunt JS,Sipes SD

    更新日期:2001-02-01 00:00:00