Heterologous prime-boost-boost immunisation of Chinese cynomolgus macaques using DNA and recombinant poxvirus vectors expressing HIV-1 virus-like particles

Background: There is renewed interest in the development of poxvirus vector-based HIV vaccines due to the protective effect observed with repeated recombinant canarypox priming with gp120 boosting in the recent Thai placebo-controlled trial. This study sought to investigate whether a heterologous prime-boost-boost vaccine regimen in Chinese cynomolgus macaques with a DNA vaccine and recombinant poxviral vectors expressing HIV virus-like particles bearing envelopes derived from the most prevalent clades circulating in sub-Saharan Africa, focused the antibody response to shared neutralising epitopes. Methods: Three Chinese cynomolgus macaques were immunised via intramuscular injections using a regimen composed of a prime with two DNA vaccines expressing clade A Env/clade B Gag followed by boosting with recombinant fowlpox virus expressing HIV-1 clade D Gag, Env and cholera toxin B subunit followed by the final boost with recombinant modified vaccinia virus Ankara expressing HIV-1 clade C Env, Gag and human complement protein C3d. We measured the macaque serum antibody responses by ELISA, enumerated T cell responses by IFN-gamma ELISpot and assessed seroneutralisation of HIV-1 using the TZM-bl beta-galactosidase assay with primary isolates of HIV-1. Results: This study shows that large and complex synthetic DNA sequences can be successfully cloned in a single step into two poxvirus vectors: MVA and FPV and the recombinant poxviruses could be grown to high titres. The vaccine candidates showed appropriate expression of recombinant proteins with the formation of authentic HIV virus-like particles seen on transmission electron microscopy. In addition the b12 epitope was shown to be held in common by the vaccine candidates using confocal immunofluorescent microscopy. The vaccine candidates were safely administered to Chinese cynomolgus macaques which elicited modest T cell responses at the end of the study but only one out of the three macaques elicited an HIV-specific antibody response. However, the antibodies did not neutralise primary isolates of HIV-1 or the V3-sensitive isolate SF162 using the TZM-bl b-galactosidase assay. Conclusions: MVA and FP9 are ideal replication-deficient viral vectors for HIV-1 vaccines due to their excellent safety profile for use in humans. This study shows this novel prime-boost-boost regimen was poorly immunogenic in Chinese cynomolgus macaques

The role of the most luminous, obscured AGN in galaxy assembly at z~2

We present HST WFC3 F160W imaging and infrared spectral energy distributions for twelve extremely luminous, obscured AGN at $1.8<z<2.7$, selected via "Hot, Dust Obscured" mid-infrared colors. Their infrared luminosities span $2-15\times10^{13}$L$_{\odot}$, making them among the most luminous objects in the Universe at $z\sim2$. In all cases the infrared emission is consistent with arising at least in most part from AGN activity. The AGN fractional luminosities are higher than those in either sub-millimeter galaxies, or AGN selected via other mid-infrared criteria. Adopting the $G$, M$_{20}$ and $A$ morphological parameters, together with traditional classification boundaries, infers that three quarters of the sample as mergers. Our sample do not, however, show any correlation between the considered morphological parameters and either infrared luminosity or AGN fractional luminosity. Moreover, their asymmetries and effective radii are distributed identically to those of massive galaxies at $z\sim2$. We conclude that our sample is not preferentially associated with mergers, though a significant merger fraction is still plausible. Instead, we propose that our sample are examples of the massive galaxy population at $z\sim2$ that harbor a briefly luminous, "flickering" AGN, and in which the $G$ and M$_{20}$ values have been perturbed, due to either the AGN, and/or the earliest formation stages of a bulge in an inside-out manner. Furthermore, we find that the mass assembly of the central black holes in our sample leads the mass assembly of any bulge component. Finally, we speculate that our sample represent a small fraction of the immediate antecedents of compact star-forming galaxies at $z\sim2$.Comment: ApJ, accepted. Updated to reflect the accepted versio

Spitzer infrared spectrometer 16μm observations of the GOODS fields

We present Spitzer 16μm imaging of the Great Observatories Origins Deep Survey (GOODS) fields. We survey 150 arcmin^2 in each of the two GOODS fields (North and South), to an average 3σ depth of 40 and 65 μJy, respectively. We detect ~1300 sources in both fields combined. We validate the photometry using the 3–24μm spectral energy distribution of stars in the fields compared to Spitzer spectroscopic templates. Comparison with ISOCAM and AKARI observations in the same fields shows reasonable agreement, though the uncertainties are large. We provide a catalog of photometry, with sources cross-correlated with available Spitzer, Chandra, and Hubble Space Telescope data. Galaxy number counts show good agreement with previous results from ISOCAM and AKARI with improved uncertainties. We examine the 16–24μm flux ratio and find that for most sources it lies within the expected locus for starbursts and infrared luminous galaxies. A color cut of S_(16)/S_(24) > 1.4 selects mostly sources which lie at 1.1 < z < 1.6, where the 24μm passband contains both the redshifted 9.7 μm silicate absorption and the minimum between polycyclic aromatic hydrocarbon emission peaks. We measure the integrated galaxy light of 16μm sources and find a lower limit on the galaxy contribution to the extragalactic background light at this wavelength to be 2.2 ± 0.2 nW m^(−2) sr^(−1)

A Deep HST Search for Escaping Lyman Continuum Flux at z~1.3: Evidence for an Evolving Ionizing Emissivity

We have obtained deep Hubble Space Telescope far-UV images of 15 starburst galaxies at z~1.3 in the GOODS fields to search for escaping Lyman continuum photons. These are the deepest far-UV images m_{AB}=28.7, 3\sigma, 1" diameter) over this large an area (4.83 arcmin^2) and provide the best escape fraction constraints for any galaxy at any redshift. We do not detect any individual galaxies, with 3\sigma limits to the Lyman Continuum (~700 \AA) flux 50--149 times fainter (in f_nu) than the rest-frame UV (1500 \AA) continuum fluxes. Correcting for the mean IGM attenuation (factor ~2), as well as an intrinsic stellar Lyman Break (~3), these limits translate to relative escape fraction limits of f_{esc,rel}<[0.03,0.21]. The stacked limit is f_{esc,rel}(3\sigma)<0.02. We use a Monte Carlo simulation to properly account for the expected distribution of IGM opacities. When including constraints from previous surveys at z~1.3 we find that, at the 95% confidence level, no more than 8% of star--forming galaxies at z~1.3 can have relative escape fractions greater than 0.50. Alternatively, if the majority of galaxies have low, but non-zero, escaping Lyman Continuum, the escape fraction can not be more than 0.04. Both the stacked limits, and the limits from the Monte Carlo simulation suggest that the average ionizing emissivity (relative to non-ionizing UV emissivity) at z~1.3 is significantly lower than has been observed in Lyman Break Galaxies (LBGs) at z~3. If the ionizing emissivity of star-forming galaxies is in fact increasing with redshift, it would help to explain the high photoionization rates seen in the IGM at z>4 and reionization of the intergalactic medium at z>6. [Abridged]Comment: Submitted to ApJ (Nov. 6) Comments Welcome. 11 pages, 8 figure

HerMES: the rest-frame UV emission and a lensing model for the z= 6.34 luminous dusty starburst galaxy HFLS3

We discuss the rest-frame ultraviolet emission from the starbursting galaxy HFLS3 at a redshift of 6.34. The galaxy was discovered in Herschel/SPIRE data due to its red color in the submillimeter wavelengths from 250 to 500 μm. Keck/NIRC2 K s -band adaptive optics imaging data showed two potential near-IR counterparts near HFLS3. Previously, the northern galaxy was taken to be in the foreground at z = 2.1, while the southern galaxy was assumed to be HFLS3's near-IR counterpart. The recently acquired Hubble/WFC3 and Advanced Camera for Surveys (ACS) imaging data show conclusively that both optically bright galaxies are in the foreground at z < 6. A new lensing model based on the Hubble imaging data and the millimeter-wave continuum emission yields a magnification factor of 2.2 ± 0.3, with a 95% confidence upper limit on the magnification of 3.5. When corrected for lensing, the instantaneous star formation rate is 1320 M ☉ yr–1, with the 95% confidence lower limit around 830 M ☉ yr–1. The dust and stellar masses of HFLS3 from the same spectral energy distribution (SED) models are at the level of 3 × 108 M ☉ and ~5 × 1010 M ☉, respectively, with large systematic uncertainties on assumptions related to the SED model. With Hubble/WFC3 images, we also find diffuse near-IR emission about 0.5 arcsec (~3 kpc) to the southwest of HFLS3 that remains undetected in the ACS imaging data. The emission has a photometric redshift consistent with either z ~ 6 or a dusty galaxy template at z ~ 2

Expanding the search for galaxies at z ~7-10 with new NICMOS Parallel Fields

We have carried out a search for galaxies at z ~ 7-10 in ~14.4 sq. arcmin of new NICMOS parallel imaging taken in the Great Observatories Origins Deep Survey (GOODS, 5.9 sq. arcmin), the Cosmic Origins Survey (COSMOS, 7.2 sq. arcmin), and SSA22 (1.3 sq. arcmin). These images reach 5 sigma sensitivities of J110 = 26.0-27.5 (AB), and combined they increase the amount of deep near-infrared data by more than 60% in fields where the investment in deep optical data has already been made. We find no z>7 candidates in our survey area, consistent with the Bouwens et al. (2008) measurements at z~7 and 9 (over 23 sq. arcmin), which predict 0.7 galaxies at z~7 and <0.03 galaxies at z~9. We estimate that 10-20% of z>7 galaxies are missed by this survey, due to incompleteness from foreground contamination by faint sources. For the case of luminosity evolution, assuming a Schecter parameterization with a typical phi* = 10^-3 Mpc^-3, we find M* > -20.0 for z~7 and M* > -20.7 for z~9 (68% confidence). This suggests that the downward luminosity evolution of LBGs continues to z~7, although our result is marginally consistent with the z~6 LF of Bouwens et al.(2006, 2007). In addition we present newly-acquired deep MMT/Megacam imaging of the z~9 candidate JD2325+1433, first presented in Henry et al. (2008). The resulting weak but significant detection at i' indicates that this galaxy is most likely an interloper at z~2.7.Comment: Accepted to ApJ. Replacement includes updated discussion of incompleteness from foreground contaminatio

A Spectroscopic Search for Leaking Lyman Continuum at Zeta Approximately 0.7

We present the results of rest-frame, UV slitless spectroscopic observations of a sample of 32 z approx. 0.7 Lyman Break Galaxy (LBG) analogs in the COSMOS field. The spectroscopic search was performed with the Solar Blind Channel (SBC) on HST. While we find no direct detections of the Lyman Continuum we achieve individual limits (3sigma) of the observed non-ionizing UV to Lyman continuum flux density ratios, f(sub nu)(1500A)/f(sub nu)(830A) of 20 to 204 (median of 73.5) and 378.7 for the stack. Assuming an intrinsic Lyman Break of 3.4 and an optical depth of Lyman continuum photons along the line of sight to the galaxy of 85% we report an upper limit for the relative escape fraction in individual galaxies of 0.02 - 0.19 and a stacked 3sigma upper limit of 0.01. We find no indication of a relative escape fraction near unity as seen in some LBGs at z approx. 3. Our UV spectra achieve the deepest limits to date at any redshift on the escape fraction in individual sources. The contrast between these z approx. 0.7 low escape fraction LBG analogs with z approx. 3 LBGs suggests that either the processes conducive to high f(sub esc) are not being selected for in the z less than or approx.1 samples or the average escape fraction is decreasing from z approx. 3 to z approx. 1. We discuss possible mechanisms which could affect the escape of Lyman continuum photon