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Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in approximately 20% of HIV-1-infected individuals, and details of their generation could provide a blueprint for effective vaccination. Here we report the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from the time of infection. The mature antibody, CH103, neutralized approximately 55% of HIV-1 isolates, and its co-crystal structure with the HIV-1 envelope protein gp120 revealed a new loop-based mechanism of CD4-binding-site recognition. Virus and antibody gene sequencing revealed concomitant virus evolution and antibody maturation. Notably, the unmutated common ancestor of the CH103 lineage avidly bound the transmitted/founder HIV-1 envelope glycoprotein, and evolution of antibody neutralization breadth was preceded by extensive viral diversification in and near the CH103 epitope. These data determine the viral and antibody evolution leading to induction of a lineage of HIV-1 broadly neutralizing antibodies, and provide insights into strategies to elicit similar antibodies by vaccination. Longitudinal sampling is used to map the evolution of an HIV-1 virus from the time of infection, and the co-evolution of a broadly neutralizing antibody in the same infected patient; the findings have important implications for HIV vaccine development. Pattern of HIV growth and antibody formation Hua-Xin Liao et al . followed the evolution of an HIV-1 virus, and the concurrent co-evolution of a CD4-binding-site broadly neutralizing antibody (BnAb), from the time of infection of a single African patient for a period of more than 3 years. The neutralizing antibody, of CH103 lineage, is a new type of BnAb that binds in a completely loop-based manner that differs from that of VRC01 class monoclonal antibodies — the CH103 lineage is less mutated, with fewer unusual macromutations and may be easier to induce. This work has implications for HIV vaccine development, suggesting viral strains that might generate broadly neutralizing antibodies within the host.

In the RV144 HIV-1 vaccine efficacy trial, IgG antibody (Ab) binding levels to variable regions 1 and 2 (V1V2) of the HIV-1 envelope glycoprotein gp120 were an inverse correlate of risk of HIV-1 infection. To determine if V1V2-specific Abs cross-react with V1V2 from different HIV-1 subtypes, if the nature of the V1V2 antigen used to asses cross-reactivity influenced infection risk, and to identify immune assays for upcoming HIV-1 vaccine efficacy trials, new V1V2-scaffold antigens were designed and tested. Protein scaffold antigens carrying the V1V2 regions from HIV-1 subtypes A, B, C, D or CRF01_AE were assayed in pilot studies, and six were selected to assess cross-reactive Abs in the plasma from the original RV144 case-control cohort (41 infected vaccinees, 205 frequency-matched uninfected vaccinees, and 40 placebo recipients) using ELISA and a binding Ab multiplex assay. IgG levels to these antigens were assessed as correlates of risk in vaccine recipients using weighted logistic regression models. Levels of Abs reactive with subtype A, B, C and CRF01_AE V1V2-scaffold antigens were all significant inverse correlates of risk (p-values of 0.0008-0.05; estimated odds ratios of 0.53-0.68 per 1 standard deviation increase). Thus, levels of vaccine-induced IgG Abs recognizing V1V2 regions from multiple HIV-1 subtypes, and presented on different scaffolds, constitute inverse correlates of risk for HIV-1 infection in the RV144 vaccine trial. The V1V2 antigens provide a link between RV144 and upcoming HIV-1 vaccine trials, and identify reagents and methods for evaluating V1V2 Abs as possible correlates of protection against HIV-1 infection. ClinicalTrials.gov NCT00223080.

Birth of a black-hole relativistic jet Two groups report observations of the X-ray source Swift J164449.3+573451, which was discovered when it triggered the Swift Burst Alert Telescope on 28 March 2011. Burrows et al . report that the source has increased in brightness in the X-ray band more than 10,000-fold since 1990, and by more than 100-fold since early 2010. They conclude that we are observing the onset of relativistic jet activity from a supermassive black hole. Zauderer et al . arrive at a similar conclusion based on their observation of a radio transient associated with the source, and extensive monitoring at centimetre to millimetre wavelengths during the first month of its evolution. They estimate the mass of the black hole at around 10 6 solar masses. Active galactic nuclei, which are powered by long-term accretion onto central supermassive black holes, produce 1 relativistic jets with lifetimes of at least one million years, and the observation of the birth of such a jet is therefore unlikely. Transient accretion onto a supermassive black hole, for example through the tidal disruption 2 , 3 of a stray star, thus offers a rare opportunity to study the birth of a relativistic jet. On 25 March 2011, an unusual transient source (Swift J164449.3+573451) was found 4 , potentially representing 5 , 6 such an accretion event. Here we report observations spanning centimetre to millimetre wavelengths and covering the first month of evolution of a luminous radio transient associated with Swift J164449.3+573451. The radio transient coincides 7 with the nucleus of an inactive galaxy. We conclude that we are seeing a newly formed relativistic outflow, launched by transient accretion onto a million-solar-mass black hole. A relativistic outflow is not predicted in this situation, but we show that the tidal disruption of a star naturally explains the observed high-energy properties and radio luminosity and the inferred rate of such events. The weaker beaming in the radio-frequency spectrum relative to γ-rays or X-rays suggests that radio searches may uncover similar events out to redshifts of z  ≈ 6.

A variant upstream of human leukocyte antigen C (HLA-C) shows the most significant genome-wide effect on HIV control in European Americans and is also associated with the level of HLA-C expression. We characterized the differential cell surface expression levels of all common HLA-C allotypes and tested directly for effects of HLA-C expression on outcomes of HIV infection in 5243 individuals. Increasing HLA-C expression was associated with protection against multiple outcomes independently of individual HLA atlelic effects in both African and European Americans, regardless of their distinct HLA-C frequencies and linkage relationships with HLA-B and HLA-A. Higher HLA-C expression was correlated with increased likelihood of cytotoxic T lymphocyte responses and frequency of viral escape mutation. In contrast, high HLA-C expression had a deleterious effect in Crohn's disease, suggesting a broader influence of HLA expression levels in human disease.

X-Rated Supernova A link between long γ-ray bursts (GRBs) and supernovae has been established, but whether there is a similar relationship between the weaker and softer X-ray flashes and supernovae is unclear. GRB/XRF 060218, spotted by the Swift satellite on 18 February this year, may supply that missing link. In the first of four papers on this novel burster, Campana et al . report the sighting of the X-ray signature of a shock break-out, possible evidence of a supernova in progress. Pian et al . report the optical discovery of a type Ic supernova 2006aj associated with GRB/XRF 060218. Soderberg et al . report radio and X-ray observations that show that XRF 060218 is 100 times less energetic than, but of a type that is ten times more common than cosmological GRBs. Mazzali et al . modelled the spectra and light curve of SN 2006aj to show that it had a much smaller explosion energy and ejected much less mass than other GRB-supernovae, suggesting that it was produced by a star with a mass was only about 20 times that of the Sun, leaving behind a neutron star, rather than a black hole. Radio and X-ray observations of X-ray flash XRF 060218, which is associated with supernova SN 2006aj, show that this event is 100 times less energetic but ten times more common than cosmological gamma-ray bursts (GRBs). The production of relativistic ejecta seems to be the key physical distinction between GRBs/XRFs and ordinary supernovae. Over the past decade, long-duration γ-ray bursts (GRBs)—including the subclass of X-ray flashes (XRFs)—have been revealed 1 , 2 , 3 to be a rare variety of type Ibc supernova. Although all these events result from the death of massive stars, the electromagnetic luminosities of GRBs and XRFs exceed those of ordinary type Ibc supernovae by many orders of magnitude. The essential physical process that causes a dying star to produce a GRB or XRF, and not just a supernova, is still unknown. Here we report radio and X-ray observations of XRF 060218 (associated 4 with supernova SN 2006aj), the second-nearest 5 , 6 GRB identified until now. We show that this event is a hundred times less energetic but ten times more common than cosmological GRBs. Moreover, it is distinguished from ordinary type Ibc supernovae by the presence of 10 48  erg coupled to mildly relativistic ejecta, along with a central engine (an accretion-fed, rapidly rotating compact source) that produces X-rays for weeks after the explosion. This suggests that the production of relativistic ejecta is the key physical distinction between GRBs or XRFs and ordinary supernovae, while the nature of the central engine (black hole or magnetar) may distinguish typical bursts from low-luminosity, spherical events like XRF 060218.

SN 2005E: untrue to type The novel properties of the faint supernova SN 2005E mean that it does not fit readily into the established supernova categories. Types Ib, Ic and II, core-collapse supernovae, are thought to form when a massive star explodes at the end of its life, and type Ia as a result of the thermonuclear explosion of an accreting white dwarf. From spectroscopic data, Perets et al . conclude that SN 2005E is helium rich, like a type Ib, and lacks the hydrogen, silicon and sulphur spectral lines typical of type Ia. But based on its presence in an 'old' stellar environment, and with a low derived ejected mass, they argue against a core-collapse origin and for an origin from a low-mass, old progenitor, probably a helium-accreting white dwarf in a binary system. Kawabata et al . see it differently. SN 2005E resembles SN 2005cz, they say, a type Ib supernova that is unusual in being found in an elliptical galaxy. Both SN 2005E and SN 2005cz, they suggest, are best explained as products of the core collapse of massive stars at the low (6–12 solar mass) end of massiveness. In the accompanying News & Views, David Branch discusses these two models in the context of the latest thinking on how stars explode. Supernovae are thought to arise through one of two processes. Type Ib/c and type II supernovae are produced when the cores of massive, short-lived stars undergo gravitational core collapse and eject a few solar masses. Type Ia supernovae are thought to form by the thermonuclear detonation of a carbon-oxygen white dwarf. Here a faint type Ib supernova, SN 2005E, is reported that seems not to have had a core-collapse origin, but perhaps arose from a low-mass, old progenitor, probably a helium-accreting white dwarf in a binary. Supernovae are thought to arise from two different physical processes. The cores of massive, short-lived stars undergo gravitational core collapse and typically eject a few solar masses during their explosion. These are thought to appear as type Ib/c and type II supernovae, and are associated with young stellar populations. In contrast, the thermonuclear detonation of a carbon-oxygen white dwarf, whose mass approaches the Chandrasekhar limit, is thought to produce type Ia supernovae 1 , 2 . Such supernovae are observed in both young and old stellar environments. Here we report a faint type Ib supernova, SN 2005E, in the halo of the nearby isolated galaxy, NGC 1032. The ‘old’ environment near the supernova location, and the very low derived ejected mass (∼0.3 solar masses), argue strongly against a core-collapse origin. Spectroscopic observations and analysis reveal high ejecta velocities, dominated by helium-burning products, probably excluding this as a subluminous 3 , 4 or a regular 1 type Ia supernova. We conclude that it arises from a low-mass, old progenitor, likely to have been a helium-accreting white dwarf in a binary. The ejecta contain more calcium than observed in other types of supernovae and probably large amounts of radioactive 44 Ti.

Past studies 1 , 2 , 3 have suggested that long-duration γ-ray bursts have a ‘standard’ energy of E γ ≈ 10 51  erg in the ultra-relativistic ejecta, after correcting for asymmetries in the explosion (‘jets’). But a group of sub-energetic bursts, including the peculiar GRB980425 associated 4 with the supernova SN1998bw ( E γ ≈ 10 48  erg), has recently been identified 2 , 3 . Here we report radio observations of GRB030329 that allow us to undertake calorimetry of the explosion. Our data require a two-component explosion: a narrow (5° opening angle) ultra-relativistic component responsible for the γ-rays and early afterglow, and a wide, mildly relativistic component that produces the radio and optical afterglow more than 1.5 days after the explosion. The total energy release, which is dominated by the wide component, is similar 1 , 2 , 3 , 5 to that of other γ-ray bursts, but the contribution of the γ-rays is energetically minor. Given the firm link 6 , 7 of GRB030329 with SN2003dh, our result indicates a common origin for cosmic explosions in which, for reasons not yet understood, the energy in the highest-velocity ejecta is extremely variable.

Supernovae with a difference Two groups working independently report the observation of mildly relativistic outflows from seemingly ordinary type Ibc and type Ic supernovae. Soderberg et al . detected luminous radio emission from the type Ibc supernova SN 2009bb, implying an expansion velocity of 0.85 times the speed of light, and a minimum energy comparable to those of the radio afterglows of nearby γ-ray bursts. Paragi et al . observed mildly relativistic expansion (at 0.6 times the speed of light or more) for a small fraction of the ejecta from the type Ic supernova SN2007gr. These discoveries are relevant to the long-standing question of what makes a small fraction of supernova explosions eject material at relativistic speeds, producing the γ-ray bursts characteristic of the explosion of a massive star. Soderberg et al . conclude that only about 1% of type Ibc supernovae harbour central engines and Paragi et al . that most or all type Ic supernovae produce mildly relativistic jets, but as they account for only a small fraction of the total energy, they are very hard to detect. Long duration γ-ray bursts mark the explosive death of some massive stars and are a rare sub-class of type Ibc supernovae. To date, central-engine-driven supernovae have been discovered exclusively through their γ-ray emission, yet it is expected that a larger population goes undetected. The discovery of luminous radio emission from the seemingly ordinary type Ibc supernova SN 2009bb, which requires a substantial relativistic outflow powered by a central engine, is now reported. Long duration γ-ray bursts (GRBs) mark 1 the explosive death of some massive stars and are a rare sub-class of type Ibc supernovae. They are distinguished by the production of an energetic and collimated relativistic outflow powered 2 by a central engine (an accreting black hole or neutron star). Observationally, this outflow is manifested 3 in the pulse of γ-rays and a long-lived radio afterglow. Until now, central-engine-driven supernovae have been discovered exclusively through their γ-ray emission, yet it is expected 4 that a larger population goes undetected because of limited satellite sensitivity or beaming of the collimated emission away from our line of sight. In this framework, the recovery of undetected GRBs may be possible through radio searches 5 , 6 for type Ibc supernovae with relativistic outflows. Here we report the discovery of luminous radio emission from the seemingly ordinary type Ibc SN 2009bb, which requires a substantial relativistic outflow powered by a central engine. A comparison with our radio survey of type Ibc supernovae reveals that the fraction harbouring central engines is low, about one per cent, measured independently from, but consistent with, the inferred 7 rate of nearby GRBs. Independently, a second mildly relativistic supernova has been reported 8 .

HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4+ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant region of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each containing mutations to enhance Fc function, was administered passively to rhesus macaques but afforded no protection against productive clinical infection while the positive control antibody CH22 IgG1 prevented infection in 4 of 6 animals. Enumeration of transmitted/founder (T/F) viruses revealed that passive infusion of each of the three antibodies significantly reduced the number of T/F genomes. Thus, some antibodies that bind HIV-1 Env but fail to neutralize virus in traditional neutralization assays may limit the number of T/F viruses involved in transmission without leading to enhancement of viral infection. For one of these mAbs, gp41 mAb 7B2, we provide the first co-crystal structure in complex with a common cyclical loop motif demonstrated to be critical for infection by other retroviruses.

The observation of a flare of radiation from the centre of an inactive galaxy fits a model of the tidal disruption of a helium-rich stellar core and its accretion onto a black hole of about three million solar masses. A flare for black holes Central supermassive black holes in distant galaxies are normally invisible to us, but sometimes their presence becomes evident in the form of flares produced by the tidal disruption of a star being accreted to the black hole. Such events are rare, and often we see only the later stages of the encounter — but here, Gezari et al . report detailed monitoring of an ultraviolet and optical flare from the nuclear region of an inactive galaxy at a redshift of 0.1696, which was first seen on 31 May 2010, peaked in July and was over by September. The observed continuum is cooler than expected for a simple accreting debris disk, but the well sampled rise and decline of the light curve follows the predicted mass-accretion rate. The black hole has about two million solar masses and the disrupted star had a helium-rich stellar core, as the authors deduced from the spectroscopic signature of ionized helium from the unbound debris. The flare of radiation from the tidal disruption and accretion of a star can be used as a marker for supermassive black holes that otherwise lie dormant and undetected in the centres of distant galaxies 1 . Previous candidate flares 2 , 3 , 4 , 5 , 6 have had declining light curves in good agreement with expectations, but with poor constraints on the time of disruption and the type of star disrupted, because the rising emission was not observed. Recently, two ‘relativistic’ candidate tidal disruption events were discovered, each of whose extreme X-ray luminosity and synchrotron radio emission were interpreted as the onset of emission from a relativistic jet 7 , 8 , 9 , 10 . Here we report a luminous ultraviolet–optical flare from the nuclear region of an inactive galaxy at a redshift of 0.1696. The observed continuum is cooler than expected for a simple accreting debris disk, but the well-sampled rise and decay of the light curve follow the predicted mass accretion rate and can be modelled to determine the time of disruption to an accuracy of two days. The black hole has a mass of about two million solar masses, modulo a factor dependent on the mass and radius of the star disrupted. On the basis of the spectroscopic signature of ionized helium from the unbound debris, we determine that the disrupted star was a helium-rich stellar core.