Epicutaneous Application of CpG Oligodeoxynucleotides with Peptide or Protein Antigen Promotes the Generation of CTL

Immunostimulatory oligodeoxynucleotides (ODN) are effective adjuvants in the induction of humoral and cellular immune responses when administered parenterally with antigen. The skin has recently become a target organ for the design of non-invasive vaccine technologies. Using ovalbumin (OVA) as a model antigen, we demonstrate that the application of ODN sequences to tape-stripped skin promotes the induction of potent cytotoxic T lymphocyte (CTL) responses to co-administered peptide. Induction of peptide-specific CTL required the presence of CpG motifs within the ODN. CTL afforded tumor protection against a tumor expressing an immunodominant OVA CTL epitope. CTL could also be induced to whole protein administered onto the skin. Differential CpG sequence activity was noted with respect to the induction of CTL to epicutaneous protein with an ODN sequence containing a poly-G motif having an optimal effect. Peptide-specific CTL could be detected in the peripheral blood as early as 6 d after a single immunization. These results highlight the potential of the bare skin as a route for vaccine development and indicate an important role for immunostimulatory ODN as adjuvants to generate functional CTL with the help of the skin immune system

Measurement of Spin Transfer Observables in Antiproton-Proton -> Antilambda-Lambda at 1.637 GeV/c

Spin transfer observables for the strangeness-production reaction Antiproton-Proton -> Antilambda-Lambda have been measured by the PS185 collaboration using a transversely-polarized frozen-spin target with an antiproton beam momentum of 1.637 GeV/c at the Low Energy Antiproton Ring at CERN. This measurement investigates observables for which current models of the reaction near threshold make significantly differing predictions. Those models are in good agreement with existing measurements performed with unpolarized particles in the initial state. Theoretical attention has focused on the fact that these models produce conflicting predictions for the spin-transfer observables D_{nn} and K_{nn}, which are measurable only with polarized target or beam. Results presented here for D_{nn} and K_{nn} are found to be in disagreement with predictions from existing models. These results also underscore the importance of singlet-state production at backward angles, while current models predict complete or near-complete triplet-state dominance.Comment: 5 pages, 3 figure

Measurement of the Eta Production in Proton Proton Collisions with the COSY Time of Flight Spectrometer

The reaction pp -> pp eta was measured at excess energies of 15 and 41 MeV at an external target of the Juelich Cooler Synchrotron COSY with the Time of Flight Spectrometer. About 25000 events were measured for the excess energy of 15 MeV and about 8000 for 41 MeV. Both protons of the process pp eta were detected with an acceptance of nearly 100% and the eta was reconstructed by the missing mass technique. For both excess energies the angular distributions are found to be nearly isotropic. In the invariant mass distributions strong deviations from the pure phase space distributions are seen.Comment: 15 pages, 14 figures, 4 table

Production of ω\omega mesons in proton-proton collisions

The cross section for the production of $\omega$ mesons in proton-proton collisions has been measured in a previously unexplored region of incident energies. Cross sections were extracted at 92 MeV and 173 MeV excess energy, respectively. The angular distribution of the $\omega$ at $\epsilon$=173 MeV is strongly anisotropic, demonstrating the importance of partial waves beyond pure s-wave production at this energy.Comment: 12 pages, 4 figures submitted to Physics Letters B v2: figure 1 added, discussion detailing the data analysis, figure 3 (fig. 2 in v1) modified in line styles and systematic errors displayed on dat

Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial

Objective: Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents. Methods: In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (≤100 kg/>100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was ≥20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and ≥75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients. Results: More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p<0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p<0.001), ACR50 (p≤0.05) and PASI75 (p<0.001); all benefits were sustained through week 52. Among patients previously treated with ≥1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change −0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change −0.13). No unexpected adverse events were observed through week 60. Conclusions: The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA, including anti-TNF-experienced PsA patients

Photoproduction of {\omega} Mesons off the Proton

The differential cross sections and unpolarized spin-density matrix elements for the reaction $\gamma p\to p\omega$ were measured using the CBELSA/TAPS experiment for initial photon energies ranging from the reaction threshold to 2.5 GeV. These observables were measured from the radiative decay of the $\omega$ meson, $\omega\to\pi^0\gamma$. The cross sections cover the full angular range and show the full extent of the $t$-channel forward rise. The overall shape of the angular distributions in the differential cross sections and unpolarized spin-density matrix elements are in fair agreement with previous data. In addition, for the first time, a beam of linearly-polarized tagged photons in the energy range from 1150 MeV to 1650 MeV was used to extract polarized spin-density matrix elements. These data were included in the Bonn-Gatchina partial wave analysis (PWA). The dominant contribution to $\omega$ photoproduction near threshold was found to be the $3/2^+$ partial wave, which is primarily due to the sub-threshold $N(1720)\,3/2^+$ resonance. At higher energies, pomeron-exchange was found to dominate whereas $\pi$-exchange remained small. These $t$-channel contributions as well as further contributions from nucleon resonances were necessary to describe the entire dataset: the $1/2^-$, $3/2^-$, and $5/2^+$ partial waves were also found to contribute significantly.Comment: 8 pages, 5 figures, accepted for publication in Physics Letters

First measurement of the helicity asymmetry for γp→pπ0\gamma p\rightarrow p\pi^0 in the resonance region

The first measurement of the helicity dependence of the photoproduction cross section of single neutral pions off protons is reported for photon energies from 600 to 2300\,MeV, covering nearly the full solid angle. The data are compared to predictions from the SAID, MAID, and BnGa partial wave analyses. Strikingly large differences between data and predictions are observed which are traced to differences in the helicity amplitudes of well known and established resonances. Precise values for the helicity amplitudes of several resonances are reported

Photoproduction of meson pairs: First measurement of the polarization observable I^s

The polarization observable I^s, a feature exclusive to the acoplanar kinematics of multi-meson final states produced via linearly polarized photons, has been measured for the first time. Results for the reaction g p -> p pi0 eta are presented for incoming photon energies between 970 MeV and 1650 MeV along with the beam asymmetry I^c. The comparably large asymmetries demonstrate a high sensitivity of I^s to the dynamics of the reaction. Fits using Bonn-Gatchina partial wave analysis demonstrate that the new polarization observables carry significant information on the contributing partial waves.Comment: 11 pages, 6 figures, v2 to appear in Phys. Lett.