Suppressive and additive effects in protection mediated by combinations of monoclonal antibodies specific for merozoite surface protein 1 of Plasmodium yoelii

<p>Abstract</p> <p>Background</p> <p>The merozoite surface protein (MSP)-1 is a target antigen of protective immunity and a malaria vaccine candidate. The nature of this protective immune response warrants further investigation: although specific antibody is thought to play a major role, the mechanisms of protection are still unclear. Monoclonal antibodies (mAbs) specific for the C-terminus of MSP-1 from <it>Plasmodium yoelii </it>have been shown previously to provide protection against challenge infection when administered by passive immunization to mice. Three protective mAbs were re-examined and, in particular, the effect of combinations of antibodies on the protection provided was studied. It was found that a combination of two antibodies can either provide additive protective effects or result in a suppression of protection. In this report the importance of antibody subclass and epitope specificity in the outcome of these passive immunization experiments are discussed.</p> <p>Methods</p> <p>The minimum protective dose (MPD) for each mAb was determined, and then combinations of antibody at their MPD were investigated for their ability to control parasitaemia and promote survival in groups of mice. Mice were inoculated over three days with the MPD and challenged with a blood stage infection of the virulent <it>P. yoelii </it>17 XL. The resultant parasitaemia was assessed daily on Giemsa-stained blood films. Following the infection the presence of MSP-1 specific antibodies in the sera was monitored, and the proliferative responses of cells in the spleen of protected mice were measured.</p> <p>Results</p> <p>Combining antibodies resulted in either an additive effect on protection, with reduced peak parasitaemia and better survival, or resulted in a suppression of protection over that achieved by a single antibody alone. An additive effect was observed when B6 and F5 that have the same isotype and similar fine specificity, were combined. However, a combination of mAb D3, an IgG2a, with either B6 or F5 (both IgG3) suppressed protection, an effect that may have been due to the combination of different isotypes or to the different fine specificity of the antibodies.</p> <p>Conclusions</p> <p>These results suggest that a combination of protective antibodies with either the same or different isotypes can produce either an additive or a suppressive effect in passive immunization. This phenomenon may be important in better understanding immunity in this experimental mouse model of malaria.</p

Measurement of the Higgs boson inclusive and differential fiducial production cross sections in the diphoton decay channel with pp collisions at s \sqrt{s} = 13 TeV

The measurements of the inclusive and differential fiducial cross sections of the Higgs boson decaying to a pair of photons are presented. The analysis is performed using proton-proton collisions data recorded with the CMS detector at the LHC at a centre-of-mass energy of 13 TeV and corresponding to an integrated luminosity of 137 fb$^{−1}$. The inclusive fiducial cross section is measured to be ${\sigma}_{\textrm{fid}}={73.4}_{-5.3}^{+5.4}{\left(\textrm{stat}\right)}_{-2.2}^{+2.4}\left(\textrm{syst}\right)$ fb, in agreement with the standard model expectation of 75.4 ± 4.1 fb. The measurements are also performed in fiducial regions targeting different production modes and as function of several observables describing the diphoton system, the number of additional jets present in the event, and other kinematic observables. Two double differential measurements are performed. No significant deviations from the standard model expectations are observed.[graphic not available: see fulltext

Azimuthal anisotropy of dijet events in PbPb collisions at sNN \sqrt{s_{\textrm{NN}}} = 5.02 TeV

AbstractThe path-length dependent parton energy loss within the dense partonic medium created in lead-lead collisions at a nucleon-nucleon center-of-mass energy of $\sqrt{s_{\textrm{NN}}}$ = 5.02 TeV is studied by determining the azimuthal anisotropies for dijets with high transverse momentum. The data were collected by the CMS experiment in 2018 and correspond to an integrated luminosity of 1.69 nb$^{−1}$. For events containing back-to-back jets, correlations in relative azimuthal angle and pseudorapidity (η) between jets and hadrons, and between two hadrons, are constructed. The anisotropies are expressed as the Fourier expansion coefficients v$_{n}$, n = 2–4 of these azimuthal distributions. The dijet v$_{n}$ values are extracted from long-range (1.5 < |∆η| < 2.5) components of these correlations, which suppresses the background contributions from jet fragmentation processes. Positive dijet v$_{2}$ values are observed which increase from central to more peripheral events, while the v$_{3}$ and v$_{4}$ values are consistent with zero within experimental uncertainties.[graphic not available: see fulltext

Search for nonresonant pair production of highly energetic Higgs bosons decaying to bottom quarks

A search for nonresonant Higgs boson (H) pair production via gluon and vector boson (V) fusion is performed in the four-bottom-quark final state, using proton-proton collision data at 13 TeV corresponding to 138 fb$^{-1}$ collected by the CMS experiment at the LHC. The analysis targets Lorentz-boosted H pairs identified using a graph neural network. It constrains the strengths relative to the standard model of the H self-coupling and the quartic VVHH couplings, ${\kappa_{2\mathrm{V}}}$, excluding ${\kappa_{2\mathrm{V}}} =$ 0 for the first time, with a significance of 6.3 standard deviations when other H couplings are fixed to their standard model values.A search for nonresonant Higgs boson ($H$) pair production via gluon and vector boson ($V$) fusion is performed in the four-bottom-quark final state, using proton-proton collision data at 13 TeV corresponding to 138 fb$^{−1}$ collected by the CMS experiment at the LHC. The analysis targets Lorentz-boosted $H$ pairs identified using a graph neural network. It constrains the strengths relative to the standard model of the $H$ self-coupling and the quartic VVHH couplings, $κ_{2V}$, excluding $κ_{2V} = 0$ for the first time, with a significance of 6.3 standard deviations when other H couplings are fixed to their standard model values.A search for nonresonant Higgs boson (H) pair production via gluon and vector boson (V) fusion is performed in the four-bottom-quark final state, using proton-proton collision data at 13 TeV corresponding to 138  fb-1 collected by the CMS experiment at the LHC. The analysis targets Lorentz-boosted H pairs identified using a graph neural network. It constrains the strengths relative to the standard model of the H self-coupling and the quartic VVHH couplings, κ2V, excluding κ2V=0 for the first time, with a significance of 6.3 standard deviations when other H couplings are fixed to their standard model values.A search for nonresonant Higgs boson ($H$) pair production via gluon and vector boson ($V$) fusion is performed in the four-bottom-quark final state, using proton-proton collision data at 13 TeV corresponding to 138 fb$^{−1}$ collected by the CMS experiment at the LHC. The analysis targets Lorentz-boosted $H$ pairs identified using a graph neural network. It constrains the strengths relative to the standard model of the $H$ self-coupling and the quartic VVHH couplings, $κ_{2V}$, excluding $κ_{2V} = 0$ for the first time, with a significance of 6.3 standard deviations when other H couplings are fixed to their standard model values.A search for nonresonant Higgs boson (H) pair production via gluon and vector boson (V) fusion is performed in the four-bottom-quark final state, using proton-proton collision data at 13 TeV corresponding to 138  fb-1 collected by the CMS experiment at the LHC. The analysis targets Lorentz-boosted H pairs identified using a graph neural network. It constrains the strengths relative to the standard model of the H self-coupling and the quartic VVHH couplings, κ2V, excluding κ2V=0 for the first time, with a significance of 6.3 standard deviations when other H couplings are fixed to their standard model values.A search for nonresonant Higgs boson ($H$) pair production via gluon and vector boson ($V$) fusion is performed in the four-bottom-quark final state, using proton-proton collision data at 13 TeV corresponding to 138 fb$^{−1}$ collected by the CMS experiment at the LHC. The analysis targets Lorentz-boosted $H$ pairs identified using a graph neural network. It constrains the strengths relative to the standard model of the $H$ self-coupling and the quartic VVHH couplings, $κ_{2V}$, excluding $κ_{2V} = 0$ for the first time, with a significance of 6.3 standard deviations when other H couplings are fixed to their standard model values.A search for nonresonant Higgs boson (H) pair production via gluon and vector boson (V) fusion is performed in the four-bottom-quark final state, using proton-proton collision data at 13 TeV corresponding to 138  fb-1 collected by the CMS experiment at the LHC. The analysis targets Lorentz-boosted H pairs identified using a graph neural network. It constrains the strengths relative to the standard model of the H self-coupling and the quartic VVHH couplings, κ2V, excluding κ2V=0 for the first time, with a significance of 6.3 standard deviations when other H couplings are fixed to their standard model values.A search for nonresonant Higgs boson ($H$) pair production via gluon and vector boson ($V$) fusion is performed in the four-bottom-quark final state, using proton-proton collision data at 13 TeV corresponding to 138 fb$^{−1}$ collected by the CMS experiment at the LHC. The analysis targets Lorentz-boosted $H$ pairs identified using a graph neural network. It constrains the strengths relative to the standard model of the $H$ self-coupling and the quartic VVHH couplings, $κ_{2V}$, excluding $κ_{2V} = 0$ for the first time, with a significance of 6.3 standard deviations when other H couplings are fixed to their standard model values.A search for nonresonant Higgs boson (H) pair production via gluon and vector boson (V) fusion is performed in the four-bottom-quark final state, using proton-proton collision data at 13 TeV corresponding to 138  fb-1 collected by the CMS experiment at the LHC. The analysis targets Lorentz-boosted H pairs identified using a graph neural network. It constrains the strengths relative to the standard model of the H self-coupling and the quartic VVHH couplings, κ2V, excluding κ2V=0 for the first time, with a significance of 6.3 standard deviations when other H couplings are fixed to their standard model values.A search for nonresonant Higgs boson ($H$) pair production via gluon and vector boson ($V$) fusion is performed in the four-bottom-quark final state, using proton-proton collision data at 13 TeV corresponding to 138 fb$^{−1}$ collected by the CMS experiment at the LHC. The analysis targets Lorentz-boosted $H$ pairs identified using a graph neural network. It constrains the strengths relative to the standard model of the $H$ self-coupling and the quartic VVHH couplings, $κ_{2V}$, excluding $κ_{2V} = 0$ for the first time, with a significance of 6.3 standard deviations when other H couplings are fixed to their standard model values.A search for nonresonant Higgs boson (H) pair production via gluon and vector boson (V) fusion is performed in the four-bottom-quark final state, using proton-proton collision data at 13 TeV corresponding to 138  fb-1 collected by the CMS experiment at the LHC. The analysis targets Lorentz-boosted H pairs identified using a graph neural network. It constrains the strengths relative to the standard model of the H self-coupling and the quartic VVHH couplings, κ2V, excluding κ2V=0 for the first time, with a significance of 6.3 standard deviations when other H couplings are fixed to their standard model values.A search for nonresonant Higgs boson (H) pair production via gluon and vector boson (V) fusion is performed in the four-bottom-quark final state, using proton-proton collision data at 13 TeV corresponding to 138 fb$^{-1}$ collected by the CMS experiment at the LHC. The analysis targets Lorentz-boosted H pairs identified using a graph neural network. It constrains the strengths relative to the standard model of the H self-coupling and the quartic VVHH couplings, $\kappa_{2V}$, excluding $\kappa_{2V}$ = 0 for the first time, with a significance of 6.3 standard deviations when other H couplings are fixed to their standard model values

Search for pair production of vector-like quarks in leptonic final states in proton-proton collisions at s \sqrt{s} = 13 TeV

A search is presented for vector-like T and B quark-antiquark pairs produced in proton-proton collisions at a center-of-mass energy of 13 TeV. Data were collected by the CMS experiment at the CERN LHC in 2016–2018, with an integrated luminosity of 138 fb$^{−1}$. Events are separated into single-lepton, same-sign charge dilepton, and multi-lepton channels. In the analysis of the single-lepton channel a multilayer neural network and jet identification techniques are employed to select signal events, while the same-sign dilepton and multilepton channels rely on the high-energy signature of the signal to distinguish it from standard model backgrounds. The data are consistent with standard model background predictions, and the production of vector-like quark pairs is excluded at 95% confidence level for T quark masses up to 1.54 TeV and B quark masses up to 1.56 TeV, depending on the branching fractions assumed, with maximal sensitivity to decay modes that include multiple top quarks. The limits obtained in this search are the strongest limits to date for $\textrm{T}\overline{\textrm{T}}$ production, excluding masses below 1.48 TeV for all decays to third generation quarks, and are the strongest limits to date for $\textrm{B}\overline{\textrm{B}}$ production with B quark decays to tW.[graphic not available: see fulltext

Search for top squarks in the four-body decay mode with single lepton final states in proton-proton collisions at s= \sqrt{s}= 13 TeV

A search for the pair production of the lightest supersymmetric partner of the top quark, the top squark ($\tilde{\mathrm{t}}_{1}$), is presented. The search targets the four-body decay of the $\tilde{\mathrm{t}}_{1}$, which is preferred when the mass difference between the top squark and the lightest supersymmetric particle is smaller than the mass of the W boson. This decay mode consists of a bottom quark, two other fermions, and the lightest neutralino ($\tilde{\chi}_{1}^{0}$), which is assumed to be the lightest supersymmetric particle. The data correspond to an integrated luminosity of 138 fb$^{-1}$ of proton-proton collisions at a center-of-mass energy of 13 TeV collected by the CMS experiment at the CERN LHC. Events are selected using the presence of a high-momentum jet, an electron or muon with low transverse momentum, and a significant missing transverse momentum. The signal is selected based on a multivariate approach that is optimized for the difference between $m(\tilde{\mathrm{t}}_{1})$ and $m(\tilde{\chi}_{1}^{0})$. The contribution from leading background processes is estimated from data. No significant excess is observed above the expectation from standard model processes. The results of this search exclude top squarks at 95% confidence level for masses up to 480 and 700 GeV for $m(\tilde{\mathrm{t}}_{1}) - m(\tilde{\chi}_{1}^{0}) =$ 10 and 80 GeV, respectively.A search for the pair production of the lightest supersymmetric partner of the top quark, the top squark (${\overset{\sim }{\textrm{t}}}_1$), is presented. The search targets the four-body decay of the ${\overset{\sim }{\textrm{t}}}_1$, which is preferred when the mass difference between the top squark and the lightest supersymmetric particle is smaller than the mass of the W boson. This decay mode consists of a bottom quark, two other fermions, and the lightest neutralino (${\overset{\sim }{\chi}}_1^0$), which is assumed to be the lightest supersymmetric particle. The data correspond to an integrated luminosity of 138 fb$^{−1}$ of proton-proton collisions at a center-of-mass energy of 13 TeV collected by the CMS experiment at the CERN LHC. Events are selected using the presence of a high-momentum jet, an electron or muon with low transverse momentum, and a significant missing transverse momentum. The signal is selected based on a multivariate approach that is optimized for the difference between m(${\overset{\sim }{\textrm{t}}}_1$) and m(${\overset{\sim }{\chi}}_1^0$). The contribution from leading background processes is estimated from data. No significant excess is observed above the expectation from standard model processes. The results of this search exclude top squarks at 95% confidence level for masses up to 480 and 700 GeV for m(${\overset{\sim }{\textrm{t}}}_1$) − m(${\overset{\sim }{\chi}}_1^0$) = 10 and 80 GeV, respectively.[graphic not available: see fulltext]A search for the pair production of the lightest supersymmetric partner of the top quark, the top squark ($\tilde{\mathrm{t}}_1$), is presented. The search targets the four-body decay of the $\tilde{\mathrm{t}}_1$, which is preferred when the mass difference between the top squark and the lightest supersymmetric particle is smaller than the mass of the W boson. This decay mode consists of a bottom quark, two other fermions, and the lightest neutralino ($\tilde{\chi}^0_1$), which is assumed to be the lightest supersymmetric particle. The data correspond to an integrated luminosity of 138 fb$^{-1}$ of proton-proton collisions at a center-of-mass energy of 13 TeV collected by the CMS experiment at the CERN LHC. Events are selected using the presence of a high-momentum jet, an electron or muon with low transverse momentum, and a significant missing transverse momentum. The signal is selected based on a multivariate approach that is optimized for the difference between $m(\tilde{\mathrm{t}}_1)$ and $m(\tilde{\chi}^0_1)$. The contribution from leading background processes is estimated from data. No significant excess is observed above the expectation from standard model processes. The results of this search exclude top squarks at 95% confidence level for masses up to 480 and 700 GeV for $m(\tilde{\mathrm{t}}_1) - m(\tilde{\chi}^0_1$) = 10 and 80 GeV, respectively

Search for nonresonant Higgs boson pair production in the four leptons plus twob jets final state in proton-proton collisions at s \sqrt{s} = 13 TeV

The first search for nonresonant production of Higgs boson pairs (HH) with one H decaying into four leptons and the other into a pair of b quarks is presented, using proton-proton collisions recorded at a center-of-mass energy of $\sqrt{s}$ = 13 TeV by the CMS experiment. The analyzed data correspond to an integrated luminosity of 138 fb$^{−1}$. A 95% confidence level upper limit of 32.4 is set on the signal strength modifier μ, defined as the ratio of the observed HH production rate in the $\textrm{HH}\to {\textrm{ZZ}}^{\ast}\textrm{b}\overline{\textrm{b}}\to 4\ell \textrm{b}\overline{\textrm{b}}$ decay channel to the standard model (SM) expectation. Possible modifications of the H trilinear coupling λ$_{HHH}$ with respect to the SM value are investigated. The coupling modifier κ$_{λ}$, defined as λ$_{HHH}$ divided by its SM prediction, is constrained to be within the observed (expected) range −8.8 (−9.8) < κ$_{λ}$< 13.4 (15.0) at 95% confidence level.[graphic not available: see fulltext

Search for long-lived particles decaying to a pair of muons in proton-proton collisions at s \sqrt{s} = 13 TeV

An inclusive search for long-lived exotic particles decaying to a pair of muons is presented. The search uses data collected by the CMS experiment at the CERN LHC in proton-proton collisions at $\sqrt{s}$ = 13 TeV in 2016 and 2018 and corresponding to an integrated luminosity of 97.6 fb$^{−1}$. The experimental signature is a pair of oppositely charged muons originating from a common secondary vertex spatially separated from the pp interaction point by distances ranging from several hundred μm to several meters. The results are interpreted in the frameworks of the hidden Abelian Higgs model, in which the Higgs boson decays to a pair of long-lived dark photons Z$_{D}$, and of a simplified model, in which long-lived particles are produced in decays of an exotic heavy neutral scalar boson. For the hidden Abelian Higgs model with m(Z$_{D}$) greater than 20 GeV and less than half the mass of the Higgs boson, they provide the best limits to date on the branching fraction of the Higgs boson to dark photons for cτ(Z$_{D}$) (varying with m(Z$_{D}$)) between 0.03 and ≈0.5 mm, and above ≈0.5 m. Our results also yield the best constraints on long-lived particles with masses larger than 10 GeV produced in decays of an exotic scalar boson heavier than the Higgs boson and decaying to a pair of muons.[graphic not available: see fulltext

Search for CPCP violation in ttH and tH production in multilepton channels in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceThe charge-parity (CP) structure of the Yukawa interaction between the Higgs (H) boson and the top quark is measured in a data sample enriched in the t$\overline{\textrm{t}}$H and tH associated production, using 138 fb$^{−1}$ of data collected in proton-proton collisions at $\sqrt{s}$ = 13 TeV by the CMS experiment at the CERN LHC. The study targets events where the H boson decays via H → WW or H → ττ and the top quarks decay via t → Wb: the W bosons decay either leptonically or hadronically, and final states characterized by the presence of at least two leptons are studied. Machine learning techniques are applied to these final states to enhance the separation of CP -even from CP -odd scenarios. Two-dimensional confidence regions are set on κ$_{t}$ and $\overset{\sim }{\kappa } _{t}$, which are respectively defined as the CP -even and CP -odd top-Higgs Yukawa coupling modifiers. No significant fractional CP -odd contributions, parameterized by the quantity |${f}_{CP}^{\textrm{Htt}}$| are observed; the parameter is determined to be |${f}_{CP}^{\textrm{Htt}}$| = 0.59 with an interval of (0.24, 0.81) at 68% confidence level. The results are combined with previous results covering the H → ZZ and H → γγ decay modes, yielding two- and one-dimensional confidence regions on κ$_{t}$ and $\overset{\sim }{\kappa } _{t}$, while |${f}_{CP}^{\textrm{Htt}}$| is determined to be |${f}_{CP}^{\textrm{Htt}}$| = 0.28 with an interval of |${f}_{CP}^{\textrm{Htt}}$| < 0.55 at 68% confidence level, in agreement with the standard model CP -even prediction of |${f}_{CP}^{\textrm{Htt}}$| = 0.[graphic not available: see fulltext

Measurement of inclusive and differential cross sections for single top quark production in association with a W boson in proton-proton collisions at s \sqrt{s} = 13 TeV

Measurements of the inclusive and normalised differential cross sections are presented for the production of single top quarks in association with a W boson in proton-proton collisions at a centre-of-mass energy of 13 TeV. The data used were recorded with the CMS detector at the LHC during 2016–2018, and correspond to an integrated luminosity of 138 fb$^{−1}$. Events containing one electron and one muon in the final state are analysed. For the inclusive measurement, a multivariate discriminant, exploiting the kinematic properties of the events is used to separate the signal from the dominant $\textrm{t}\overline{\textrm{t}}$ background. A cross section of $79.2\pm 0.9{\left(\textrm{stat}\right)}_{-8.0}^{+7.7}\left(\textrm{syst}\right)\pm 1.2\left(\textrm{lumi}\right)$ pb is obtained, consistent with the predictions of the standard model. For the differential measurements, a fiducial region is defined according to the detector acceptance, and the requirement of exactly one jet coming from the fragmentation of a bottom quark. The resulting distributions are unfolded to particle level and agree with the predictions at next-to-leading order in perturbative quantum chromodynamics.[graphic not available: see fulltext