Why did the HIV vaccine STEP trial fail?

Summaries of newsworthy papers in Nature and Nature research journals including: Origin of raindrop size revealed, Geoscience: Full circle, Possible mechanism for blood cancer type, Fast-flowing ice streams mould their beds, A genetic susceptibility locus for follicular lymphoma and Neuroscience: Exploring exploration


For papers that will be published online on 20 July 2009
This press release is copyrighted to the Nature journals mentioned below.

This press release contains:

· Summaries of newsworthy papers:

Medicine: Why did the HIV vaccine STEP trial fail?
Physics: Origin of raindrop size revealed
Geoscience: Full circle
Nature: Possible mechanism for blood cancer type
Geoscience: Fast-flowing ice streams mould their beds
Genetics: A genetic susceptibility locus for follicular lymphoma
And finally - Neuroscience: Exploring exploration

· Mention of papers to be published at the same time with the same embargo
· Geographical listing of authors

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[1] & [2] Medicine: Why did the HIV vaccine STEP trial fail?

DOI: 10.1038/nm.1989
DOI: 10.1038/nm.1991

The failure of the recent HIV STEP trial represented a serious blow to the development of an AIDS vaccine. Two papers published this week in Nature Medicine rule out a leading explanation for this failure.

In the STEP trial, participants were vaccinated with a weakened form of a common cold virus (Ad5) which was altered to carry three HIV genes. It was believed that stimulating the immune system with these weakened HIV genes would lead to a more aggressive response to HIV if and when the participant was exposed to it. However, the vaccine resulted in increased HIV-1 acquisition, particularly if the volunteer had high levels of Ad5-neutralizing antibodies, which are often observed.

Since HIV-1 targets the body’s T cells, the STEP trial results led to the hypothesis that vaccination of individuals with high levels of Ad5 antibodies had an increase in their T cell numbers, which served as targets for the HIV-1 infection.

The two groups lead by Dan Barouch and Michael Betts found that there is no correlation between baseline levels of Ad5-specific neutralizing antibodies and Ad5-specific T cell responses. Moreover, individuals with high levels of Ad5 antibodies do not develop higher Ad5-specific immune responses after vaccination compared to individuals with low levels of Ad5 antibodies.

Although these findings indicate no direct role for the Ad5-specific T cells in increasing HIV-1 susceptibility in the STEP trial, the true reason for its failure remain a mystery.

Author contacts:

Michael Betts (University of Pennsylvania, Philadelphia, PA, USA) Author paper [1]
Tel: +1 215 573 2773; E-mail: [email protected]

Dan Barouch (Beth Israel Deaconess Medical Center, Boston, MA, USA) Author paper [2]
Tel: +1 617 735 4485; E-mail: [email protected]

[3] Physics: Origin of raindrop size revealed

DOI: 10.1038/nphys1340

The sizes of raindrops are caused by the break up of individual droplets, reports a study published online this week in Nature Physics. This is a much simpler mechanism than was previously thought.

When raindrops hit the ground they do so in a wide range of sizes. It was thought that this size distribution was the result of a complex series of interactions between the droplets as they fall. But by analyzing high-speed movies of falling water droplets, Emmanuel Villermaux and Benjamin Bossa show that this distribution is caused by the fragmentation of individual, non-interacting raindrops.

The movies demonstrate that as an initially spherical droplet falls, it gradually flattens out into a pancake shape. As it gets wider and thinner, it eventually captures the air in front of it to form the shape of an upturned bag. Finally, as the bag inflates to a certain size, it breaks apart into many smaller droplets - droplets whose size distribution mimics that of natural rainfall.

Author contacts:

Emmanuel Villermaux (Aix-Marseille Université, Marseille, France)
Tel: +33 4 96 13 97 42; E-mail: [email protected]

Benjamin Bossa (Aix-Marseille Université, Marseille, France)
Tel: +33 4 96 13 97 00; E-mail: [email protected]

[4] Geoscience: Full circle

DOI: 10.1038/ngeo583

Dust clouds from China were transported more than one full circle around the globe in 13 days, according to a study published online in Nature Geoscience. The findings illustrate that dust clouds generated in one region could have effects on many parts of the world.

Itsushi Uno and colleagues used satellite and model data to show that a storm in China’s Taklimakan Desert in May 2007 generated dust clouds that were lifted 8-10 km above the Earth’s surface, and transported more than one full circle around the Earth. When the dust reached the north-western Pacific Ocean for a second time, the subsidence of a high-pressure system caused the dust-laden clouds to descend into the lower atmosphere and some of the dust was then deposited in the ocean.

The analysis also suggests that the dust particles may have triggered ice formation in the high-altitude clouds.

Author contact:

Itsushi Uno (Kyushu University, Japan)
Tel: +81 92 583 7771; E-mail: [email protected]

[5] Nature: Possible mechanism for blood cancer type

DOI: 10.1038/nature08240

A new molecular mechanism may underlie a diverse group of blood cancers called myelodysplastic syndromes, a Nature paper suggests.

Human cells contain two complete sets of chromosomes, one from each parent, but in certain cancers, both copies of particular chromosomes can come from the same parent. Patients with a particular type of bone marrow cancer inherit two copies of part of chromosome 11 from a single parent, Seishi Ogawa and colleagues report. This part of the chromosome contains a mutated version of the gene C-CBL, they show. The C-CBL mutations are oncogenic, causing cultured connective tissue cells to become cancerous. The study suggests that wild-type C-CBL acts as a tumour suppressor gene, but that the gain-of-function mutations identified in this type of cancer turn it into a cancer-causing oncogene.

Author contact:

Seishi Ogawa (University of Tokyo, Japan)
Tel: +81 3 5800 9046; E-mail: [email protected]

[6] Geoscience: Fast-flowing ice streams mould their beds

DOI: 10.1038/ngeo581

The sediments beneath fast-flowing ice streams change dynamically within decades, reports a study published online in this week’s Nature Geoscience. The work shows conclusively that elongated ridges in the sediment bed - called mega-scale glacial lineations - are characteristic of regions of fast ice flow.

Edward King and colleagues collected radar data that reveal the ice-sediment interface beneath Rutford Ice Stream, a glacier in West Antarctica. They identified mega-scale glacial lineations in the sedimentary bed that have identical characteristics to sediment beds of ancient ice sheets. Using seismic data, the researchers conclude that beneath fast-flowing ice streams the sediment bed changes relatively quickly. Most of the discharge from large ice sheetsm - such as the one covering Antarctica - is channeled through such fast-flowing streams, and the properties of the underlying sediments can affect the speed of ice flow.

In an accompanying Backstory, Edward King writes about his experience of camping in Antarctica to collect the data.

Author contact:
Edward King (British Antarctic Survey, Cambridge, UK)
Tel: + 44 1 223 221 580; E-mail: [email protected]

[7] Genetics: A genetic susceptibility locus for follicular lymphoma

DOI: 10.1038/ng.419

A common genetic variant is associated with risk for follicular lymphoma (FL), according to a study published online in this week’s Nature Genetics.

Lymphomas are cancers that arise in immune system cells, and are classified into two different types: Hodgkin and non-Hodgkin lymphoma (NHL). The risk of developing NHL increases with age, and about 1 out of 4 cases of NHL is follicular lymphoma. The overall survival rate of FL varies widely, but about 20% of cases die early in the course of the disease.

In this study, Christine Skibola and colleagues analyzed the genomes of thousands of individuals with NHL. They report that a genetic variant on chromosome 6p21 is significantly associated with FL.

Author contact:

Christine Skibola (University of California, Berkeley, CA, USA)
Tel: +1 510 643 5041; E-mail: [email protected]

[8] Neuroscience: Exploring exploration

DOI 10.1038/nn.2342

In the face of uncertainty about the outcomes of our decisions, how do we choose between sticking with what we’ve been doing and trying a new approach? In a study published online this week in Nature Neuroscience, Michael Frank and colleagues show that a gene regulating dopamine breakdown is predictive of how likely people are to explore alternative strategies when uncertain about current strategy.

Previous studies had found that the COMT gene in the prefrontal cortex, the region of the brain directly behind the forehead, regulates levels of the neurotransmitter dopamine. People with one form of this gene - valine-encoding - have a more efficient version of the COMT enzyme, resulting in lower dopamine levels, than those with another form of the gene - methionine-encoding.

Frank and colleagues asked participants, genotyped for their COMT gene, to perform a simple task of deciding when to stop a clock. Subjects were given points based on the timing of their responses. However, they were not told whether an early or late response would be more rewarding, and had to discover the best response strategy by trial and error. When participants were uncertain about what the best strategy to garner points was, those carrying the methionine type gene were more likely to explore alternative strategies than those carrying the valine type gene.

The scientists created a mathematical model to quantify how much people with the different types of COMT are likely to explore alternate strategies with different levels of uncertainty. Their work reinforces the body of evidence that suggests that genes controlling dopamine function in the brain critically affect our decision-making.

Author contacts:

Michael Frank (Brown University, Providence, RI, USA)
Tel: +1 401 863 6872; E-mail: [email protected]

Matthew Rushworth (University of Oxford, UK) News & Views Author
Tel: +44 165 271 358; E-mail: [email protected]


Items from other Nature journals to be published online at the same time and with the same embargo:

Nature (http://www.nature.com/nature)

[9] A tuneable topological insulator in the spin helical Dirac transport regime
DOI: 10.1038/nature08234

NATURE BIOTECHNOLOGY (http://www.nature.com/naturebiotechnology)

[10] Therapeutic IgG4 antibodies engage in Fab-arm exchange with endogenous human IgG4 in vivo
DOI: 10.1038/nbt.1553

NATURE CELL BIOLOGY (http://www.nature.com/naturecellbiology)

[11] Identification of chromosome sequence motifs that mediate meiotic pairing and synapsis in C. elegans
DOI: 10.1038/ncb1904

[12] A regulatory pathway involving Notch1/beta-catenin/Isl1 determines cardiac progenitor cell fate
DOI: 10.1038/ncb1906

[13] VHL loss causes spindle misorientation and chromosome instability
DOI: 10.1038/ncb1912

[14] Axonal elongation triggered by stimulus-induced local translation of a polarity complex protein
DOI: 10.1038/ncb1916

NATURE CHEMICAL BIOLOGY (http://www.nature.com/nchembio)

[15] Discovery of proteinaceous N-modification in lysine biosynthesis of Thermus thermophilus

NATURE CHEMISTRY (http://www.nature.com/nchem)

[16] Size-specific catalytic activity of platinum clusters enhances oxygen reduction reactions
DOI: 10.1038/nchem.288

[17] Spin transition in a four-coordinate iron oxide
DOI: 10.1038/nchem.289

NATURE GENETICS (http://www.nature.com/naturegenetics)

[18] A mouse model of the ATR-Seckel Syndrome reveals that replicative stress during embryogenesis limits mammalian lifespan
DOI: 10.1038/ng.420

NATURE GEOSCIENCE (http://www.nature.com/ngeo)

[19] Early martian mantle overturn inferred from isotopic composition of nakhlite meteorites
DOI: 10.1038/ngeo579

NATURE IMMUNOLOGY (http://www.nature.com/natureimmunology)

[20] Targeting of the GTPase Irgm1 to the phagosomal membrane via PtdIns(3,4)P2 and PtdIns(3,4,5)P3 promotes immunity to mycobacteria
DOI: 10.1038/ni.1759

NATURE METHODS (http://www.nature.com/nmeth)

[21] Robust, high-throughput solution structural analyses by small angle X-ray scattering (SAXS)
DOI: 10.1038/nmeth.1353

[22] Virtual Terminator nucleotides for next generation DNA sequencing
DOI: 10.1038/nmeth.1354

[23] Digital RNA Allelotyping Reveals Tissue-specific and Allele-specific Gene Expression in Human
DOI: 10.1038/nmeth.1357

Nature NEUROSCIENCE (http://www.nature.com/natureneuroscience)

[24] Targeted disruption of cocaine-activated nucleus accumbens neurons prevents context-specific sensitization
DOI 10.1038/nn.2364

[25] Balanced gene regulation by an embryonic brain noncoding RNA is critical for GABA circuitry in adult hippocampus
DOI 10.1038/nn.2371

[26] SAP97 and CASK mediate sorting of NMDA receptors through a previously unknown secretory pathway
DOI 10.1038/nn.2362

NATURE PHOTONICS (http://www.nature.com/nphoton)

[27] Silicon nanostructure cloak operating at optical frequencies
DOI: 10.1038/nphoton.2009.117

Nature PHYSICS (http://www.nature.com/naturephysics)

[28] Measurement of quantum noise in a single-electron transistor near the quantum limit
DOI: 10.1038/nphys1339

[29] Quantum computation and quantum-state engineering driven by dissipation
DOI: 10.1038/nphys1342

[30] Mimicking celestial mechanics in metamaterials
DOI: 10.1038/nphys1338

Nature STRUCTURAL & MOLECULAR BIOLOGY (http://www.nature.com/natstructmolbiol)

[31] Coding sequence targeting by MicC RNA reveals bacterial mRNA silencing downstream of translational initiation
DOI: 10.1038/nsmb.1631

[32] Intrinsic histone-DNA interactions are not the major determinant of nucleosome positions in vivo
DOI: 10.1038/nsmb.1636

[33 Avid interactions underlie the Lys63-linked polyubiquitin binding specificities observed for UBA domains
DOI: 10.1038/nsmb.1637

[34] Structural insights into host GTPase isoform selection by a family of bacterial GEF mimics
DOI: 10.1038/nsmb.1647



The following list of places refers to the whereabouts of authors on the papers numbered in this release. The listing may be for an author's main affiliation, or for a place where they are working temporarily. Please see the PDF of the paper for full details.

New South Wales: 19

Vienna: 17, 29

Brussels: 19

Vancouver: 7

Beijing: 4, 34
Shanghai: 9

Copenhagen: 29

Marseille: 3
Paris: 3

Berlin: 31
Freiburg: 7
Garching: 29
Heidelberg: 7

Dublin: 31

Fukuoka: 4
Gunma: 5
Hiroshima: 5
Hyogo: 15
Ibaraki: 4, 5
Kanagawa: 5
Kyoto: 15, 17
Mitaka: 16
Saitama: 5
Sakai: 20
Shizuoka: 15
Tochigi: 5
Tokyo: 4, 5, 15, 17
Yokohama: 15, 16

Seoul: 14

Amsterdam: 10
Leiden: 2
Utrecht: 10

Auckland: 26

Madrid: 18

Basel: 13
Villigen: 9
Zurich: 9, 13

Taipei: 5

Cambridge: 6
Durham: 6
Hertfordshire: 10
Norwich: 31

Phoenix: 7
Tucson: 8
Berkeley: 7, 9, 11, 21, 30
Davis: 19
Irvine: 14
La Jolla: 21, 23, 32
Los Angeles: 5
Palo Alto: 26
Richmond: 11
San Francisco: 7, 12
Santa Clara: 23
Fort Collins: 33
New Haven: 20, 32
Athens: 21
Suwanee: 21
Chicago: 25, 26
Ruston: 30
Baltimore: 18, 24, 33
College Park: 33
Boston: 2, 9, 11, 23, 32
Cambridge: 2, 22, 23
New Hampshire
Hanover: 28
New Jersey
Princeton: 9
New York
Ithaca: 27
New York: 14, 26
Cleveland: 25
Philadelphia: 1, 2
West Point: 1, 2
Rhode Island
Providence: 8, 26
Memphis: 18
Oak Ridge: 17
Dallas: 34
Houston: 19, 24, 28
Hampton: 4
Richmond: 23


For media inquiries relating to embargo policy for all the Nature Research Journals:

Rachel Twinn (Nature London)
Tel: +44 20 7843 4658; E-mail: [email protected]

Neda Afsarmanesh (Nature New York)
Tel: +1 212 726 9231; E-mail: [email protected]

Ruth Francis (Head of Press, Nature, London)
Tel: +44 20 7843 4562; E-mail: [email protected]

For media inquiries relating to editorial content/policy for the Nature Research Journals, please contact the journals individually:

Nature Biotechnology (New York)
Craig Mak
Tel: +1 212 726 9284; E-mail: [email protected]

Nature Cell Biology (London)
Bernd Pulverer
Tel: +44 20 7843 4892; E-mail: [email protected]

Nature Chemical Biology (Boston)
Andrea Garvey
Tel: +1 617 475 9241, E-mail: [email protected]

Nature Chemistry (London)
Stuart Cantrill
Tel: +44 20 7014 4018; E-mail: [email protected]

Nature Genetics (New York)
Myles Axton
Tel: +1 212 726 9324; E-mail: [email protected]

Nature Geoscience (London)
Heike Langenberg
Tel: +44 20 7843 4042; E-mail: [email protected]

Nature Immunology (New York)
Laurie Dempsey
Tel: +1 212 726 9372; E-mail: [email protected]

Nature Materials (London)
Vincent Dusastre
Tel: +44 20 7843 4531; E-mail: [email protected]

Nature Medicine (New York)
Juan Carlos Lopez
Tel: +1 212 726 9325; E-mail: [email protected]

Nature Methods (New York)
Hugh Ash
Tel: +1 212 726 9627; E-mail: [email protected]

Nature Neuroscience (New York)
Kalyani Narasimhan
Tel: +1 212 726 9319; E-mail: [email protected]

Nature Photonics (Tokyo)
Oliver Graydon
Tel: +81 3 3267 8776; E-mail: [email protected]

Nature Physics (London)
Alison Wright
Tel: +44 20 7843 4555; E-mail: [email protected]

Nature Structural & Molecular Biology (New York)
Michelle Montoya
Tel: +1 212 726 9326; E-mail: [email protected]

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Published: 20 Jul 2009

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