Epitope-specific antibody responses differentiate COVID-19 outcomes and variants of concern

BACKGROUND. The role of humoral immunity in COVID-19 is not fully understood, owing, in large part, to the complexity of antibodies produced in response to the SARS-CoV-2 infection. There is a pressing need for serology tests to assess patient-specific antibody response and predict clinical outcome. METHODS. Using SARS-CoV-2 proteome and peptide microarrays, we screened 146 COVID-19 patients’ plasma samples to identify antigens and epitopes. This enabled us to develop a master epitope array and an epitope-specific agglutination assay to gauge antibody responses systematically and with high resolution. RESULTS. We identified linear epitopes from the spike (S) and nucleocapsid (N) proteins and showed that the epitopes enabled higher resolution antibody profiling than the S or N protein antigen. Specifically, we found that antibody responses to the S-811–825, S-881–895, and N-156–170 epitopes negatively or positively correlated with clinical severity or patient survival. Moreover, we found that the P681H and S235F mutations associated with the coronavirus variant of concern B.1.1.7 altered the specificity of the corresponding epitopes. CONCLUSION. Epitope-resolved antibody testing not only affords a high-resolution alternative to conventional immunoassays to delineate the complex humoral immunity to SARS-CoV-2 and differentiate between neutralizing and non-neutralizing antibodies, but it also may potentially be used to predict clinical outcome. The epitope peptides can be readily modified to detect antibodies against variants of concern in both the peptide array and latex agglutination formats. FUNDING. Ontario Research Fund (ORF) COVID-19 Rapid Research Fund, Toronto COVID-19 Action Fund, Western University, Lawson Health Research Institute, London Health Sciences Foundation, and Academic Medical Organization of Southwestern Ontario (AMOSO) Innovation Fund

Large-scale interaction profiling of PDZ domains through proteomic peptide-phage display using human and viral phage peptidomes

The human proteome contains a plethora of short linear motifs (SLiMs) that serve as binding interfaces for modular protein domains. Such interactions are crucial for signaling and other cellular processes, but are difficult to detect because of their low to moderate affinities. Here we developed a dedicated approach, proteomic peptide-phage display (ProP-PD), to identify domain-SLiM interactions. Specifically, we generated phage libraries containing all human and viral C-terminal peptides using custom oligonucleotide microarrays. With these libraries we screened the nine PSD-95/ Dlg/ZO-1 (PDZ) domains of human Densin-180, Erbin, Scribble, and Disks large homolog 1 for peptide ligands. We identified several known and putative interactions potentially relevant to cellular signaling pathways and confirmed interactions between fulllength Scribble and the target proteins β-PIX, plakophilin-4, and guanylate cyclase soluble subunit a-2 using colocalization and coimmunoprecipitation experiments. The affinities of recombinant Scribble PDZ domains and the synthetic peptides representing the C termini of these proteins were in the 1- to 40-μM range. Furthermore, we identified several well-established host-virus protein- protein interactions, and confirmed that PDZ domains of Scribble interact with the C terminus of Tax-1 of human T-cell leukemia virus with micromolar affinity. Previously unknown putative viral protein ligands for the PDZ domains of Scribble and Erbin were also identified. Thus, we demonstrate that our ProP-PD libraries are useful tools for probing PDZ domain interactions. The method can be extended to interrogate all potential eukaryotic, bacterial, and viral SLiMs and we suggest it will be a highly valuable approach for studying cellular and pathogen-host protein-protein interactions

Search for directional associations between Baikal Gigaton Volume Detector neutrino-induced cascades and high-energy astrophysical sources

Baikal-GVD has recently published its first measurement of the diffuse astrophysical neutrino flux, performed using high-energy cascade-like events. We further explore the Baikal-GVD cascade dataset collected in 2018-2022, with the aim to identify possible associations between the Baikal-GVD neutrinos and known astrophysical sources. We leverage the relatively high angular resolution of the Baikal-GVD neutrino telescope (2-3 deg.), made possible by the use of liquid water as the detection medium, enabling the study of astrophysical point sources even with cascade events. We estimate the telescope's sensitivity in the cascade channel for high-energy astrophysical sources and refine our analysis prescriptions using Monte-Carlo simulations. We primarily focus on cascades with energies exceeding 100 TeV, which we employ to search for correlation with radio-bright blazars. Although the currently limited neutrino sample size provides no statistically significant effects, our analysis suggests a number of possible associations with both extragalactic and Galactic sources. Specifically, we present an analysis of an observed triplet of neutrino candidate events in the Galactic plane, focusing on its potential connection with certain Galactic sources, and discuss the coincidence of cascades with several bright and flaring blazars.Comment: 10 pages, 3 figure

Large neutrino telescope Baikal-GVD: recent status

The Baikal-GVD is a deep-underwater neutrino telescope being constructed in Lake Baikal. After the winter 2023 deployment campaign the detector consists of 3456 optical modules installed on 96 vertical strings. The status of the detector and progress in data analysis are discussed in present report. The Baikal-GVD data collected in 2018-2022 indicate the presence of cosmic neutrino flux in high-energy cascade events consistent with observations by the IceCube neutrino telescope. Analysis of track-like events results in identification of first high-energy muon neutrino candidates. These and other results from 2018-2022 data samples are reviewed in this report

Studies of the ambient light of deep Baikal waters with Baikal-GVD

The Baikal-GVD neutrino detector is a deep-underwater neutrino telescope under construction and recently after the winter 2023 deployment it consists of 3456 optical modules attached on 96 vertical strings. This 3-dimensional array of photo-sensors allows to observe ambient light in the vicinity of the Baikal-GVD telescope that is associated mostly with water luminescence. Results on time and space variations of the luminescent activity are reviewed based on data collected in 2018-2022

Monitoring of optical properties of deep waters of Lake Baikal in 2021-2022

We present the results of the two-year (2021-2022) monitoring of absorption and scattering lengths of light with wavelength 400-620 nm within the effective volume of the deep underwater neutrino telescope Baikal-GVD, which were measured by a device Baikal-5D No.2. The Baikal-5D No.2. was installed during the 2021 winter expedition at a depth of 1180 m. The absorption and scattering lengths were measured every week in 9 spectral points. The device Baikal-5D No.2 also has the ability to measure detailed scattering and absorption spectra. The data obtained make it possible to estimate the range of changes in the absorption and scattering lengths over a sufficiently long period of time and to investigate the relationship between the processes of changes in absorption and scattering. An analysis was made of changes in absorption and scattering spectra for the period 2021-2022

Combined searches for the production of supersymmetric top quark partners in proton–proton collisions at √s=13Te

A combination of searches for top squark pair production using proton–proton collision data at a center-of-mass energy of 13TeV at the CERN LHC, corresponding to an integrated luminosity of 137fb$^{-1}$ collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on the model, the combined result excludes a top squark mass up to 1325GeV for a massless neutralino, and a neutralino mass up to 700GeV for a top squark mass of 1150GeV. Top squarks with masses from 145 to 295GeV, for neutralino masses from 0 to 100GeV, with a mass difference between the top squark and the neutralino in a window of 30GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420GeV

Measurements of production cross sections of WZ and same-sign WW boson pairs in association with two jets in proton-proton collisions at √s = 13 TeV

The first measurements of production cross sections of polarized same-sign W$^{±}$ W$^{±}$ boson pairs in proton-proton collisions are reported. The measurements are based on a data sample collected with the CMS detector at the LHC at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 137fb$^{-1}$. Events are selected by requiring exactly two same-sign leptons, electrons or muons, moderate missing transverse momentum, and two jets with a large rapidity separation and a large dijet mass to enhance the contribution of same-sign W$^{±}$ W$^{±}$ scattering events. An observed (expected) 95% confidence level upper limit of 1.17 (0.88) fbis set on the production cross section for longitudinally polarized same-sign W$^{±}$ W$^{±}$ boson pairs. The electroweak production of same-sign W$^{±}$ W$^{±}$ boson pairs with at least one of the W bosons longitudinally polarized is measured with an observed (expected) significance of 2.3 (3.1) standard deviations

Search for decays of the 125 GeV Higgs boson into a Z boson and a ρ or ϕ meson

Decays of the 125 GeV Higgs boson into a Z boson and a ρ^0(770) or ϕ(1020) meson are searched for using proton-proton collision data collected by the CMS experiment at the LHC at √s = 13 TeV. The analysed data set corresponds to an integrated luminosity of 137 fb⁻¹. Events are selected in which the Z boson decays into a pair of electrons or a pair of muons, and the ρ and ϕ mesons decay into pairs of pions and kaons, respectively. No significant excess above the background model is observed. As different polarization states are possible for the decay products of the Z boson and ρ or ϕ mesons, affecting the signal acceptance, scenarios in which the decays are longitudinally or transversely polarized are considered. Upper limits at the 95% confidence level on the Higgs boson branching fractions into Zρ and Zϕ are determined to be 1.04–1.31% and 0.31–0.40%, respectively, where the ranges reflect the considered polarization scenarios; these values are 740–940 and 730–950 times larger than the respective standard model expectations. These results constitute the first experimental limits on the two decay channels