| 1. |
- Pollard, R. B., et al.
(författare)
-
Safety and efficacy of the peptide-based therapeutic vaccine for HIV-1, Vacc-4x : A phase 2 randomised, double-blind, placebo-controlled trial
- 2014
-
Ingår i: The Lancet - Infectious diseases. - 1473-3099 .- 1474-4457. ; 14:4, s. 291-300
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Present combination antiretroviral therapy (cART) alone does not cure HIV infection and requires lifelong drug treatment. The potential role of HIV therapeutic vaccines as part of an HIV cure is under consideration. Our aim was to assess the efficacy, safety, and immunogenicity of Vacc-4x, a peptide-based HIV-1 therapeutic vaccine targeting conserved domains on p24Gag, in adults infected with HIV-1. Methods: Between July, 2008, and June, 2010, we did a multinational double-blind, randomised, phase 2 study comparing Vacc-4x with placebo. Participants were adults infected with HIV-1 who were aged 18-55 years and virologically suppressed on cART (viral load <50 copies per mL) with CD4 cell counts of 400 × 106 cells per L or greater. The trial was done at 18 sites in Germany, Italy, Spain, the UK, and the USA. Participants were randomly assigned (2:1) to Vacc-4x or placebo. Group allocation was masked from participants and investigators. Four primary immunisations, weekly for 4 weeks, containing Vacc-4x (or placebo) were given intradermally after administration of adjuvant. Booster immunisations were given at weeks 16 and 18. At week 28, cART was interrupted for up to 24 weeks. The coprimary endpoints were cART resumption and changes in CD4 counts during treatment interruption. Analyses were by modified intention to treat: all participants who received one intervention. Furthermore, safety, viral load, and immunogenicity (as measured by ELISPOT and proliferation assays) were assessed. The 52 week follow-up period was completed in June, 2011. For the coprimary endpoints the proportion of participants who met the criteria for cART resumption was analysed with a logistic regression model with the treatment effect being assessed in a model including country as a covariate. This study is registered with ClinicalTrials.gov, number NCT00659789. Findings: 174 individuals were screened; because of slow recruitment, enrolment stopped with 136 of a planned 345 participants and 93 were randomly assigned to receive Vacc-4x and 43 to receive placebo. There were no differences between the two groups for the primary efficacy endpoints in those participants who stopped cART at week 28. Of the participants who resumed cART, 30 (34%) were in the Vacc-4x group and 11 (29%) in the placebo group, and percentage changes in CD4 counts were not significant (mean treatment difference -5·71, 95% CI -13·01 to 1·59). However, a significant difference in viral load was noted for the Vacc-4x group both at week 48 (median 23 100 copies per mL Vacc-4x vs 71 800 copies per mL placebo; p=0·025) and week 52 (median 19 550 copies per mL vs 51 000 copies per mL; p=0·041). One serious adverse event, exacerbation of multiple sclerosis, was reported as possibly related to study treatment. Vacc-4x was immunogenic, inducing proliferative responses in both CD4 and CD8 T-cell populations. Interpretation: The proportion of participants resuming cART before end of study and change in CD4 counts during the treatment interruption showed no benefit of vaccination. Vacc-4x was safe, well tolerated, immunogenic, seemed to contribute to a viral-load setpoint reduction after cART interruption, and might be worth consideration in future HIV-cure investigative strategies. Funding: Norwegian Research Council GLOBVAC Program and Bionor Pharma ASA.
|
|
| 2. |
|
|
| 3. |
- Mottola, S., et al.
(författare)
-
The rotation state of 67P/Churyumov-Gerasimenko from approach observations with the OSIRIS cameras on Rosetta
- 2014
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 569, s. L2-
-
Tidskriftsartikel (refereegranskat)abstract
- Aims. Approach observations with the Optical, Spectroscopic, and Infrared Remote Imaging System (OSIRIS) experiment onboard Rosetta are used to determine the rotation period, the direction of the spin axis, and the state of rotation of comet 67P's nucleus. Methods. Photometric time series of 67P have been acquired by OSIRIS since the post wake-up commissioning of the payload in March 2014. Fourier analysis and convex shape inversion methods have been applied to the Rosetta data as well to the available ground-based observations. Results. Evidence is found that the rotation rate of 67P has significantly changed near the time of its 2009 perihelion passage, probably due to sublimation-induced torque. We find that the sidereal rotation periods P-1 = 12.76129 +/- 0.00005 h and P2 = 12.4043 +/- 0.0007 h for the apparitions before and after the 2009 perihelion, respectively, provide the best fit to the observations. No signs of multiple periodicity are found in the light curves down to the noise level, which implies that the comet is presently in a simple rotation state around its axis of largest moment of inertia. We derive a prograde rotation model with spin vector J2000 ecliptic coordinates lambda = 65 degrees +/- 15 degrees, beta = + 59 degrees +/- 15 degrees, corresponding to equatorial coordinates RA = 22 degrees, Dec = +76 degrees. However, we find that the mirror solution, also prograde, at lambda = 275 degrees +/- 15 degrees, beta = + 50 degrees +/- 15 degrees (or RA = 274 degrees, Dec = +27 degrees), is also possible at the same confidence level, due to the intrinsic ambiguity of the photometric problem for observations performed close to the ecliptic plane.
|
|
| 4. |
- Keller, H. U., et al.
(författare)
-
E-Type Asteroid (2867) Steins as Imaged by OSIRIS on Board Rosetta
- 2010
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 327:5962, s. 190-193
-
Tidskriftsartikel (refereegranskat)abstract
- The European Space Agency's Rosetta mission encountered the main-belt asteroid (2867) Steins while on its way to rendezvous with comet 67P/Churyumov-Gerasimenko. Images taken with the OSIRIS (optical, spectroscopic, and infrared remote imaging system) cameras on board Rosetta show that Steins is an oblate body with an effective spherical diameter of 5.3 kilometers. Its surface does not show color variations. The morphology of Steins is dominated by linear faults and a large 2.1-kilometer-diameter crater near its south pole. Crater counts reveal a distinct lack of small craters. Steins is not solid rock but a rubble pile and has a conical appearance that is probably the result of reshaping due to Yarkovsky-O'Keefe-Radzievskii-Paddack (YORP) spin-up. The OSIRIS images constitute direct evidence for the YORP effect on a main-belt asteroid.
|
|
| 5. |
- Sierks, H., et al.
(författare)
-
Images of Asteroid 21 Lutetia : A Remnant Planetesimal from the Early Solar System
- 2011
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 334:6055, s. 487-490
-
Tidskriftsartikel (refereegranskat)abstract
- Images obtained by the Optical, Spectroscopic, and Infrared Remote Imaging System (OSIRIS) cameras onboard the Rosetta spacecraft reveal that asteroid 21 Lutetia has a complex geology and one of the highest asteroid densities measured so far, 3.4 +/- 0.3 grams per cubic centimeter. The north pole region is covered by a thick layer of regolith, which is seen to flow in major landslides associated with albedo variation. Its geologically complex surface, ancient surface age, and high density suggest that Lutetia is most likely a primordial planetesimal. This contrasts with smaller asteroids visited by previous spacecraft, which are probably shattered bodies, fragments of larger parents, or reaccumulated rubble piles.
|
|
| 6. |
- Vincent, J. -B, et al.
(författare)
-
Physical Properties of Craters on Asteroid (21) Lutetia
- 2011
-
Ingår i: Lunar and Planetary Institute Science Conference Abstracts.
-
Konferensbidrag (refereegranskat)abstract
- This abstract presents the physical properties of craters derived from the measurement of depth/diameter ratios on asteroid (21) Lutetia. We show how the d/D ratio varies in different regions and how it can be used to better understand the processes that affected the surface.
|
|
