Pre-Clinical Evaluation of a Replication-Competent Recombinant Adenovirus Serotype 4 Vaccine Expressing Influenza H5 Hemagglutinin

Influenza virus remains a significant health and social concern in part because of newly emerging strains, such as avian H5N1 virus. We have developed a prototype H5N1 vaccine using a recombinant, replication-competent Adenovirus serotype 4 (Ad4) vector, derived from the U.S. military Ad4 vaccine strain, to express the hemagglutinin (HA) gene from A/Vietnam/1194/2004 influenza virus (Ad4-H5-Vtn). Our hypothesis is that a mucosally-delivered replicating Ad4-H5-Vtn recombinant vector will be safe and induce protective immunity against H5N1 influenza virus infection and disease pathogenesis.The Ad4-H5-Vtn vaccine was designed with a partial deletion of the E3 region of Ad4 to accommodate the influenza HA gene. Replication and growth kinetics of the vaccine virus in multiple human cell lines indicated that the vaccine virus is attenuated relative to the wild type virus. Expression of the HA transgene in infected cells was documented by flow cytometry, western blot analysis and induction of HA-specific antibody and cellular immune responses in mice. Of particular note, mice immunized intranasally with the Ad4-H5-Vtn vaccine were protected against lethal H5N1 reassortant viral challenge even in the presence of pre-existing immunity to the Ad4 wild type virus.Several non-clinical attributes of this vaccine including safety, induction of HA-specific humoral and cellular immunity, and efficacy were demonstrated using an animal model to support Phase 1 clinical trial evaluation of this new vaccine

Sensitivity of the T2K accelerator-based neutrino experiment with an Extended run to 20×102120\times10^{21} POT

18 pages, 4 figures18 pages, 4 figures18 pages, 4 figures18 pages, 4 figures18 pages, 4 figuresRecent measurements at the T2K experiment indicate that CP violation in neutrino mixing may be observed in the future by long-baseline neutrino oscillation experiments. We explore the physics program of an extension to the currently approved T2K running of $7.8\times 10^{21}$ protons-on-target to $20\times 10^{21}$ protons-on-target,aiming at initial observation of CP violation with 3$\,\sigma$ or higher significance for the case of maximum CP violation. With accelerator and beam line upgrades, as well as analysis improvements, this program would occur before the next generation of long-baseline neutrino oscillation experiments that are expected to start operation in 2026.We acknowledge the support of MEXT, Japan; NSERC (Grant No. SAPPJ-2014-00031), NRC and CFI, Canada; CEA and CNRS/IN2P3, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; RSF, RFBR and MES, Russia; MINECO and ERDF funds, Spain; SNSF and SERI, Switzerland; STFC, UK; and DOE, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, and GridPP in the United Kingdom. In addition, participation of individual researchers and institutions has been further supported by funds from ERC (FP7), H2020 Grant No. RISE-GA644294-JENNIFER, EU; JSPS, Japan; Royal Society, UK; and the DOE Early Career program, USA. CNRS/IN2P3: Centre National de la Recherche ScientifiqueInstitut National de Physique Nucleaire et de Physique des Particules RSF: Russian Science Foundation MES: Ministry of Education and Science, Russia ERDF: European Regional Development Fund SNSF: Swiss National Science Foundation SER (should be SERI): State Secretariat for Education, Research and Innovatio

Proposal for an Extended Run of T2K to 20×102120\times10^{21} POT

68 pages, 31 figures68 pages, 31 figures68 pages, 31 figuresRecent measurements by the T2K neutrino oscillation experiment indicate that CP violation in neutrino mixing may be observed in the future by long-baseline neutrino oscillation experiments. We propose an extension to the currently approved T2K running from 7.8\times 10^{21}~\mbox{POT} to 20\times 10^{21}~\mbox{POT}, aiming at initial observation of CP violation with 3$\,\sigma$ or higher significance for the case of maximum CP violation. The program also contains a measurement of mixing parameters, $\theta_{23}$ and $\Delta m^2_{32}$, with a precision of 1.7$^\circ$ or better and 1%, respectively. With accelerator and beamline upgrades, as well as analysis improvements, this program would occur before the next generation of long-baseline neutrino oscillation experiments that are expected to start operation in 2026

Measurement of the single pi(0) production rate in neutral current neutrino interactions on water

The single π0 production rate in neutral current neutrino interactions on water in a neutrino beam with a peak neutrino energy of 0.6 GeV has been measured using the PØD, one of the subdetectors of the T2K near detector. The production rate was measured for data taking periods when the PØD contained water (2.64×10(20) protons-on-target) and also periods without water (3.49×10(20) protons-on-target). A measurement of the neutral current single π0 production rate on water is made using appropriate subtraction of the production rate with water in from the rate with water out of the target region. The subtraction analysis yields 106 ± 41 ± 69 signal events where the uncertainties are statistical (stat.) and systematic (sys.) respectively. This is consistent with the prediction of 157 events from the nominal simulation. The measured to expected ratio is 0.68 ± 0.26 (stat) ± 0.44 (sys) ± 0.12 (flux). The nominal simulation uses a flux integrated cross section of 7.63×10(−39)cm(2) per nucleon with an average neutrino interaction energy of 1.3 GeV

First Measurement of the Muon Neutrino Charged Current Single Pion Production Cross Section on Water with the T2K Near Detector

The T2K off-axis near detector, ND280, is used to make the first differential cross section measurements of muon neutrino charged current single positive pion production on a water target at energies ${\sim}0.8$ GeV. The differential measurements are presented as a function of muon and pion kinematics, in the restricted phase-space defined by $p_{\pi^+}>200$MeV/c, $p_{\mu^-}>200$MeV/c, $\cos \theta_{\pi^+}>0.3$ and $\cos \theta_{\mu^-}>0.3$. The total flux integrated $\nu_\mu$ charged current single positive pion production cross section on water in the restricted phase-space is measured to be $\langle\sigma\rangle_\phi=4.25\pm0.48 (\mathrm{stat})\pm1.56 (\mathrm{syst})\times10^{-40} \mathrm{cm}^{2}/\mathrm{nucleon}$. The total cross section is consistent with the NEUT prediction ($5.03\times10^{-40} \mathrm{cm}^{2}/\mathrm{nucleon}$) and 2$\sigma$ lower than the GENIE prediction ($7.68\times10^{-40} \mathrm{cm}^{2}/\mathrm{nucleon}$). The differential cross sections are in good agreement with the NEUT generator. The GENIE simulation reproduces well the shapes of the distributions, but over-estimates the overall cross section normalization

Characterization of nuclear effects in muon-neutrino scattering on hydrocarbon with a measurement of final-state kinematics and correlations in charged-current pionless interactions at T2K

This paper reports measurements of final-state proton multiplicity, muon and proton kinematics, and their correlations in charged-current pionless neutrino interactions, measured by the T2K ND280 near detector in its plastic scintillator (C8H8) target. The data were taken between years 2010 and 2013, corresponding to approximately 6 × 1020 protons on target. Thanks to their exploration of the proton kinematics and of imbalances between the proton and muon kinematics, the results offer a novel probe of the nuclear-medium effects most pertinent to the (sub-)GeV neutrino-nucleus interactions that are used in accelerator-based long-baseline neutrino oscillation measurements. These results are compared to many neutrino-nucleus interaction models which all fail to describe at least part of the observed phase space. In case of events without a proton above a detection threshold in the final state, a fully consistent implementation of the local Fermi gas model with multinucleon interactions gives the best description of the data. In the case of at least one proton in the final state, the spectral function model agrees well with the data, most notably when measuring the kinematic imbalance between the muon and the proton in the plane transverse to the incoming neutrino. Within the models considered, only the existence of multinucleon interactions are able to describe the extracted cross section within regions of high transverse kinematic imbalance. The effect of final-state interactions is also discussed

Search for light sterile neutrinos with the T2K far detector Super-Kamiokande at a baseline of 295 km

We perform a search for light sterile neutrinos using the data from the T2K far detector at a baseline of 295 km, with an exposure of 14.7ð7.6Þ × 1020 protons on target in neutrino (antineutrino) mode. A selection of neutral-current interaction samples is also used to enhance the sensitivity to sterile mixing. No evidence of sterile neutrino mixing in the 3 þ 1 model was found from a simultaneous fit to the charged-current muon, electron and neutral-current neutrino samples. We set the most stringent limit on the sterile oscillation amplitude sin2 θ24 for the sterile neutrino mass splitting Δm241 < 3 × 10−3 eV2=c4

Search for CP Violation in Neutrino and Antineutrino Oscillations by the T2K Experiment with 2.2 x 10(21) Protons on Target

The T2K experiment measures muon neutrino disappearance and electron neutrino appearance in accelerator-produced neutrino and antineutrino beams. With an exposure of $14.7(7.6)\times 10^{20}$ protons on target in neutrino (antineutrino) mode, 89 $\nu_e$ candidates and 7 anti-$\nu_e$ candidates were observed while 67.5 and 9.0 are expected for $\delta_{CP}=0$ and normal mass ordering. The obtained $2\sigma$ confidence interval for the $CP$ violating phase, $\delta_{CP}$, does not include the $CP$-conserving cases ($\delta_{CP}=0,\pi$). The best-fit values of other parameters are $\sin^2\theta_{23} = 0.526^{+0.032}_{-0.036}$ and $\Delta m^2_{32}=2.463^{+0.071}_{-0.070}\times10^{-3} \mathrm{eV}^2/c^4$.Comment: 9 pages, 6 figure

Search for neutral-current induced single photon production at the ND280 near detector in T2K

Neutrino neutral-current (NC) induced single photon production is a sub-leading order process for accelerator-based neutrino beam experiments including T2K. It is, however, an important process to understand because it is a background for electron (anti)neutrino appearance oscillation experiments. Here, we performed the first search of this process below 1 GeV using the fine-grained detector at the T2K ND280 off-axis near detector. By reconstructing single photon kinematics from electron-positron pairs, we achieved 95% pure gamma ray sample from 5.738 x 10(20) protons-on-targets neutrino mode data. We do not find positive evidence of NC induced single photon production in this sample. We set the model-dependent upper limit on the cross-section for this process, at 0.114 x 10(-38) cm(2) (90% C.L.) per nucleon, using the J-PARC off-axis neutrino beam with an average energy of similar to 0.6 GeV. This is the first limit on this process below 1 GeV which is important for current and future oscillation experiments looking for electron neutrino appearance oscillation signals