939 research outputs found
Systemic and Mucosal Immune Responses to Sublingual or Intramuscular Human Papilloma Virus Antigens in Healthy Female Volunteers
The sublingual route has been proposed as a needle-free option to induce systemic and mucosal immune protection against viral infections. In a translational study of systemic and mucosal humoral immune responses to sublingual or systemically administered viral antigens, eighteen healthy female volunteers aged 19–31 years received three immunizations with a quadravalent Human Papilloma Virus vaccine at 0, 4 and 16 weeks as sublingual drops (SL, n = 12) or intramuscular injection (IM, n = 6). IM antigen delivery induced or boosted HPV-specific serum IgG and pseudovirus-neutralizing antibodies, HPV-specific cervical and vaginal IgG, and elicited circulating IgG and IgA antibody secreting cells. SL antigens induced ∼38-fold lower serum and ∼2-fold lower cervical/vaginal IgG than IM delivery, and induced or boosted serum virus neutralizing antibody in only 3/12 subjects. Neither route reproducibly induced HPV-specific mucosal IgA. Alternative delivery systems and adjuvants will be required to enhance and evaluate immune responses following sublingual immunization in humans
Transient Facial Nerve Paralysis (Bell's Palsy) following Intranasal Delivery of a Genetically Detoxified Mutant of Escherichia coli Heat Labile Toxin
BACKGROUND: An association was previously established between facial nerve paralysis (Bell's palsy) and intranasal administration of an inactivated influenza virosome vaccine containing an enzymatically active Escherichia coli Heat Labile Toxin (LT) adjuvant. The individual component(s) responsible for paralysis were not identified, and the vaccine was withdrawn.
METHODOLOGY/PRINCIPAL FINDINGS: Subjects participating in two contemporaneous non-randomized Phase 1 clinical trials of nasal subunit vaccines against Human Immunodeficiency Virus and tuberculosis, both of which employed an enzymatically inactive non-toxic mutant LT adjuvant (LTK63), underwent active follow-up for adverse events using diary-cards and clinical examination. Two healthy subjects experienced transient peripheral facial nerve palsies 44 and 60 days after passive nasal instillation of LTK63, possibly a result of retrograde axonal transport after neuronal ganglioside binding or an inflammatory immune response, but without exaggerated immune responses to LTK63.
CONCLUSIONS/SIGNIFICANCE: While the unique anatomical predisposition of the facial nerve to compression suggests nasal delivery of neuronal-binding LT-derived adjuvants is inadvisable, their continued investigation as topical or mucosal adjuvants and antigens appears warranted on the basis of longstanding safety via oral, percutaneous, and other mucosal routes
Posterior Decompression and Fusion: Whole-Spine Functional and Clinical Outcomes
The mobility of the spine and the change in the angle of the curvatures are directly related to spinal pain and spinal stenosis. The aim of the study was the evaluation of morphology and mobility of the spine in patients who were subjected to decompression and posterior fusion with pedicle screws. The treatment group consisted of 20 patients who underwent posterior fixation of lumbar spine (one and two level fusion). The control group consisted of 39 healthy subjects. Mobility and curvatures of the spine were measured with a non-invasive device, the Spinal Mouse. Pain was evaluated with the Visual Analogue Scale (VAS). The Oswestry Disability Index (ODI) and the SF-36 were used to evaluate the degree of the functional disability and the quality of life, respectively. The measurements were recorded preoperatively and at 3, 6 and 12 months postoperatively. The mobility of the lumbar spine in the sagittal plane increased (p = 0.009) at 12 months compared to the measurements at 3 months. The mobility of the thoracic spine in the frontal plane increased (p = 0.009) at 12 months compared to the preoperative evaluation. The results of VAS, ODI and SF-36 PCS improved significantly (p<0.001). The levels of fusion exhibited a strong linear correlation (r = 0.651, p = 0.002) with the total trunk inclination in the upright position. Although pain, quality of life and spinal mobility in the sagittal and frontal planes significantly improved in the treatment group, these patients still had limited mobility and decreased curves/angles values compared to control group
Phase I Randomised Clinical Trial of an HIV-1CN54, Clade C, Trimeric Envelope Vaccine Candidate Delivered Vaginally
We conducted a phase 1 double-blind randomised controlled trial (RCT) of a HIV-1 envelope protein (CN54 gp140) candidate vaccine delivered vaginally to assess immunogenicity and safety. It was hypothesised that repeated delivery of gp140 may facilitate antigen uptake and presentation at this mucosal surface. Twenty two healthy female volunteers aged 18–45 years were entered into the trial, the first receiving open-label active product. Subsequently, 16 women were randomised to receive 9 doses of 100 µg of gp140 in 3 ml of a Carbopol 974P based gel, 5 were randomised to placebo solution in the same gel, delivered vaginally via an applicator. Participants delivered the vaccine three times a week over three weeks during one menstrual cycle, and were followed up for two further months. There were no serious adverse events, and the vaccine was well tolerated. No sustained systemic or local IgG, IgA, or T cell responses to the gp140 were detected following vaginal immunisations. Repeated vaginal immunisation with a HIV-1 envelope protein alone formulated in Carbopol gel was safe, but did not induce local or systemic immune responses in healthy women
Observation of the Decay Λ0b→Λ+cτ−¯ν
The first observation of the semileptonic b-baryon decay Λb0→Λc+τ-ν¯τ, with a significance of 6.1σ, is reported using a data sample corresponding to 3 fb-1 of integrated luminosity, collected by the LHCb experiment at center-of-mass energies of 7 and 8 TeV at the LHC. The τ- lepton is reconstructed in the hadronic decay to three charged pions. The ratio K=B(Λb0→Λc+τ-ν¯τ)/B(Λb0→Λc+π-π+π-) is measured to be 2.46±0.27±0.40, where the first uncertainty is statistical and the second systematic. The branching fraction B(Λb0→Λc+τ-ν¯τ)=(1.50±0.16±0.25±0.23)% is obtained, where the third uncertainty is from the external branching fraction of the normalization channel Λb0→Λc+π-π+π-. The ratio of semileptonic branching fractions R(Λc+)B(Λb0→Λc+τ-ν¯τ)/B(Λb0→Λc+μ-ν¯μ) is derived to be 0.242±0.026±0.040±0.059, where the external branching fraction uncertainty from the channel Λb0→Λc+μ-ν¯μ contributes to the last term. This result is in agreement with the standard model prediction
A study of CP violation in the decays B±→[K+K-π+π-]Dh± (h= K, π) and B±→[π+π-π+π-]Dh±
The first study of CP violation in the decay mode B±→[K+K-π+π-]Dh± , with h= K, π , is presented, exploiting a data sample of proton–proton collisions collected by the LHCb experiment that corresponds to an integrated luminosity of 9 \,fb - 1 . The analysis is performed in bins of phase space, which are optimised for sensitivity to local CP asymmetries. CP -violating observables that are sensitive to the angle γ of the Unitarity Triangle are determined. The analysis requires external information on charm-decay parameters, which are currently taken from an amplitude analysis of LHCb data, but can be updated in the future when direct measurements become available. Measurements are also performed of phase-space integrated observables for B±→[K+K-π+π-]Dh± and B±→[π+π-π+π-]Dh± decays
Measurement of lepton universality parameters in and decays
A simultaneous analysis of the and decays is performed to test muon-electron universality in
two ranges of the square of the dilepton invariant mass, . The measurement
uses a sample of beauty meson decays produced in proton-proton collisions
collected with the LHCb detector between 2011 and 2018, corresponding to an
integrated luminosity of . A sequence of multivariate
selections and strict particle identification requirements produce a higher
signal purity and a better statistical sensitivity per unit luminosity than
previous LHCb lepton universality tests using the same decay modes. Residual
backgrounds due to misidentified hadronic decays are studied using data and
included in the fit model. Each of the four lepton universality measurements
reported is either the first in the given interval or supersedes previous
LHCb measurements. The results are compatible with the predictions of the
Standard Model.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-045.html (LHCb
public pages
Observation of Cabibbo-suppressed two-body hadronic decays and precision mass measurement of the baryon
The first observation of the singly Cabibbo-suppressed
and decays
is reported, using proton-proton collision data at a centre-of-mass energy of
, corresponding to an integrated luminosity of , collected with the LHCb detector between 2016 and 2018. The
branching fraction ratios are measured to be
,
. In addition, using the
decay channel, the baryon
mass is measured to be , improving the
precision of the previous world average by a factor of four.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-011.html (LHCb
public pages
Measurement of boson production cross-section in collisions at TeV
The first measurement of the boson production cross-section at
centre-of-mass energy TeV in the forward region is reported,
using collision data collected by the LHCb experiment in year 2017,
corresponding to an integrated luminosity of . The
production cross-section is measured for final-state muons in the
pseudorapidity range . The integrated cross-section is determined to be for the di-muon invariant
mass in the range . This result and the
differential cross-section results are in good agreement with theoretical
predictions at next-to-next-to-leading order in the strong coupling.
Based on a previous LHCb measurement of the boson production
cross-section in Pb collisions at TeV, the nuclear
modification factor is measured for the first time at this
energy. The measured values are in the forward region () and
in the backward region
(), where represents the muon rapidity in
the centre-of-mass frame.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-010.html (LHCb
public pages
Study of charmonium decays to in the channels
A study of the and decays
is performed using proton-proton collisions at center-of-mass energies of 7, 8
and 13 TeV at the LHCb experiment. The invariant mass spectra from
both decay modes reveal a rich content of charmonium resonances. New precise
measurements of the and resonance parameters are
performed and branching fraction measurements are obtained for decays to
, , and resonances. In particular, the
first observation and branching fraction measurement of is reported as well as first measurements of the
and branching fractions. Dalitz plot analyses of
and decays are performed. A
new measurement of the amplitude and phase of the -wave as functions
of the mass is performed, together with measurements of the
, and parameters. Finally, the branching
fractions of decays to resonances are also measured.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-051.html (LHCb
public pages
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