Systemic Foot-and-Mouth Disease Vaccination in Cattle Promotes Specific Antibody-Secreting Cells at the Respiratory Tract and Triggers Local Anamnestic Responses upon Aerosol Infection

Foot-and-mouth disease (FMD) is a highly contagious viral disease affecting biungulate species. Commercial vaccines, formulated with inactivated FMD virus (FMDV), are regularly used worldwide to control the disease. Here, we studied the generation of antibody responses in local lymphoid tissues along the respiratory system in vaccinated and further aerosol-infected cattle. Animals immunized with a high-payload monovalent FMD vaccine developed high titers of neutralizing antibodies at 7 days postvaccination (dpv), reaching a plateau at 29 dpv. FMDV-specific antibody-secreting cells (ASC), predominantly IgM, were evident at 7 dpv in the prescapular lymph node (LN) draining the vaccination site and in distal LN draining the respiratory mucosa, although in lower numbers. At 29 dpv, a significant switch to IgG1 was clear in prescapular LN, while FMDV-specific ASC were detected in all lymphoid tissues draining the respiratory tract, mostly as IgM-secreting cells. None of the animals (n = 10) exhibited FMD symptoms after oronasal challenge at 30 dpv. Three days postinfection, a large increase in ASC numbers and rapid isotype switches to IgG1 were observed, particularly in LN-draining virus replication sites already described. These results indicate for the first time that systemic FMD vaccination in cattle effectively promotes the presence of anti-FMDV ASC in lymphoid tissues associated with the respiratory system. Oronasal infection triggered an immune reaction compatible with a local anamnestic response upon contact with the replicating FMDV, suggesting that FMD vaccination induces the circulation of virus-specific B lymphocytes, including memory B cells that differentiate into ASC soon after contact with the infectiveInstituto de VirologíaFil: Pega, Juan Franco. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Di Giacomo, Sebastián. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; ArgentinaFil: Bucafusco, Danilo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schammas, Juan Manuel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; ArgentinaFil: Malacari, Darío Amilcar. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; ArgentinaFil: Barrionuevo, Florencia Mariel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Capozzo, Alejandra Victoria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rodríguez, L.L. USDA. Agricultural Research Service. Plum Island Animal Disease Center; Estados UnidosFil: Borca, Manuel Victor. USDA. Agricultural Research Service. Plum Island Animal Disease Center; Estados UnidosFil: Perez Filgueira, Daniel Mariano. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Early Adaptive Immune Responses in the Respiratory Tract of Foot-and-Mouth Disease Virus-Infected Cattle

Foot-and-mouth disease (FMD) is a highly contagious viral disease which affects both domestic and wild biungulate species. This acute disease, caused by the FMD virus (FMDV), usually includes an active replication phase in the respiratory tract for up to 72 h postinfection, followed by hematogenous dissemination and vesicular lesions at oral and foot epithelia. The role of the early local adaptive immunity of the host in the outcome of the infection is not well understood. Here we report the kinetics of appearance of FMDV-specific antibody-secreting cells (ASC) in lymphoid organs along the respiratory tract and the spleen in cattle infected by aerosol exposure. While no responses were observed for up to 3 days postinfection (dpi), all animals developed FMDV-ASC in all the lymphoid organs studied at 4 dpi. Tracheobronchial lymph nodes were the most reactive organs at this time, and IgM was the predominant isotype, followed by IgG1. Numbers of FMDV-ASC were further augmented at 5 and 6 dpi, with an increasing prevalence in upper respiratory organs. Systemic antibody responses were slightly delayed compared with the local reaction. Also, IgM was the dominant isotype in serum at 5 dpi, coinciding with a sharp decrease of viral RNA detection in peripheral blood. These results indicate that following aerogenous administration, cattle develop a rapid and vigorous genuine local antibody response throughout the respiratory tract. Time course and isotype profiles indicate the presence of an efficient T cell-independent antibody response which drives the IgM-mediated virus clearance in cattle infected by FMDV aerosol exposure.Instituto de VirologíaFil: Pega, Juan Franco. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bucafusco, Danilo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Di Giacomo, Sebastián. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; ArgentinaFil: Schammas, Juan Manuel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; ArgentinaFil: Malacari, Darío Amilcar. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; ArgentinaFil: Capozzo, Alejandra Victoria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Arzt, J. USDA. Agricultural Research Service. Plum Island Animal Disease Center; Estados UnidosFil: Pérez Beascoeachea, C. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Dirección de Laboratorios; ArgentinaFil: Maradei, E. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Dirección de Laboratorios; ArgentinaFil: Rodríguez, L. USDA. Agricultural Research Service. Plum Island Animal Disease Center; Estados UnidosFil: Borca, Manuel Victor. USDA. Agricultural Research Service. Plum Island Animal Disease Center; Estados UnidosFil: Perez Filgueira, Daniel Mariano. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Heterogeneity in the antibody response to foot‐and‐mouth disease primo‐vaccinated calves

Foot‐and‐mouth disease (FMD) vaccines are routinely used as effective control tools in large regions worldwide and to limit outbreaks during epidemics. Vaccine‐induced protection in cattle has been largely correlated with the FMD virus (FMDV)‐specific antibodies. Genetic control of cattle immune adaptive responses has been demonstrated only for peptide antigens derived from FMDV structural proteins. Here, we quantify the heterogeneity in the antibody response of cattle primo‐vaccinated against FMD and study its association with the genetic background in Holstein and Jersey sires. A total of 377 FMDV‐seronegative calves (122 and 255 calves from 16 and 15 Holstein and Jersey sires, respectively) were included in the study. Samples were taken the day prior to primo‐vaccination and 45 days post‐vaccination (dpv). Animals received commercial tetravalent FMD single emulsion oil vaccines formulated with inactivated FMDV. Total FMDV‐specific antibody responses were studied against three viral strains included in the vaccine, and antibody titres were determined by liquid‐phase blocking ELISA. Three linear hierarchical mixed regression models, one for each strain, were formulated to assess the heterogeneity in the immune responses to vaccination. The dependent variables were the antibody titres induced against each FMDV strain at 45 dpv, whereas sire's ‘breed’ was included as a fixed effect, ‘sire’ was included as a random effect, and ‘farm’ was considered as a hierarchical factor to account for lack of independence of within herd measurements. A significant association was found between anti‐FMDV antibody responses and sire's breed, with lower immune responses found in the Jersey sires’ offspring compared with those from Holstein sires. No significant intrabreed variation was detected. In addition, farm management practices were similar in this study, and results of the serological assays were shown to be repeatable. It therefore seems plausible that differences in the immune response may be expected in the event of a mass vaccination campaigns.Instituto de VirologíaFil: Di Giacomo, Sebastián. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; ArgentinaFil: Brito, Barbara Patricia. University of California Davis. School of Veterinary Medicine. Center for Animal Diseases Modeling and Surveillance. Department of Medicine and Epidemiology; Estados UnidosFil: Perez, A.M. University of California Davis. School of Veterinary Medicine. Center for Animal Diseases Modeling and Surveillance. Department of Medicine and Epidemiology; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bucafusco, Danilo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pega, Juan Franco. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rodríguez, L. USDA. Agricultural Research Service. Plum Island Animal Disease Center; Estados UnidosFil: Borca, Manuel Victor. USDA. Agricultural Research Service. Plum Island Animal Disease Center; Estados UnidosFil: Perez Filgueira, Daniel Mariano. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Evaluation of the Safety Profile of the ASFV Vaccine Candidate ASFV-G-ΔI177L

African swine fever (ASF) is the cause of a recent pandemic that is posing a threat to much of the world swine production. The etiological agent, ASF virus (ASFV), infects domestic and wild swine, producing a variety of clinical presentations depending on the virus strain and the genetic background of the pigs infected. No commercial vaccine is currently available, although recombinant live attenuated vaccine candidates have been shown to be efficacious. In addition to determining efficacy, it is paramount to evaluate the safety profile of a live attenuated vaccine. The presence of residual virulence and the possibility of reversion to virulence are two of the concerns that must be evaluated in the development of live attenuated vaccines. Here we evaluate the safety profile of an efficacious live attenuated vaccine candidate, ASFV-G-ΔI177L. Results from safety studies showed that ASFV-G-ΔI177L remains genetically stable and phenotypically attenuated during a five-passage reversion to virulence study in domestic swine. In addition, large-scale experiments to detect virus shedding and transmission confirmed that even under varying conditions, ASFV-G-ΔI177L is a safe live attenuated vaccine

Elliptic anisotropy measurement of the f0_0(980) hadron in proton-lead collisions and evidence for its quark-antiquark composition

International audienceDespite the f$_0$(980) hadron having been discovered half a century ago, the question about its quark content has not been settled: it might be an ordinary quark-antiquark ($\mathrm{q\bar{q}}$) meson, a tetraquark ($\mathrm{q\bar{q}q\bar{q}}$) exotic state, a kaon-antikaon ($\mathrm{K\bar{K}}$) molecule, or a quark-antiquark-gluon ($\mathrm{q\bar{q}g}$) hybrid. This paper reports strong evidence that the f$_0$(980) state is an ordinary $\mathrm{q\bar{q}}$ meson, inferred from the scaling of elliptic anisotropies ($v_2$) with the number of constituent quarks ($n_\mathrm{q}$), as empirically established using conventional hadrons in relativistic heavy ion collisions. The f$_0$(980) state is reconstructed via its dominant decay channel f$_0$(980) $\to$$\pi^+\pi^-$, in proton-lead collisions recorded by the CMS experiment at the LHC, and its $v_2$ is measured as a function of transverse momentum ($p_\mathrm{T}$). It is found that the $n_q$ = 2 ($\mathrm{q\bar{q}}$ state) hypothesis is favored over $n_q$ = 4 ($\mathrm{q\bar{q}q\bar{q}}$ or $\mathrm{K\bar{K}}$ states) by 7.7, 6.3, or 3.1 standard deviations in the $p_\mathrm{T}$$\lt$ 10, 8, or 6 GeV/$c$ ranges, respectively, and over $n_\mathrm{q}$ = 3 ($\mathrm{q\bar{q}g}$ hybrid state) by 3.5 standard deviations in the $p_\mathrm{T}$$\lt$ 8 GeV/$c$ range. This result represents the first determination of the quark content of the f$_0$(980) state, made possible by using a novel approach, and paves the way for similar studies of other exotic hadron candidates

Extracting the speed of sound in the strongly interacting matter created in ultrarelativistic lead-lead collisions at the LHC

International audienceUltrarelativistic nuclear collisions create a strongly interacting state of hot and dense quark-gluon matter that exhibits a remarkable collective flow behavior with minimal viscous dissipation. To gain deeper insights into its intrinsic nature and fundamental degrees of freedom, we extracted the speed of sound in this medium created using lead-lead (PbPb) collisions at a center-of-mass energy per nucleon pair of 5.02 TeV. The data were recorded by the CMS experiment at the CERN LHC and correspond to an integrated luminosity of 0.607 nb$^{-1}$. The measurement is performed by studying the multiplicity dependence of the average transverse momentum of charged particles emitted in head-on PbPb collisions. Our findings reveal that the speed of sound in this matter is nearly half the speed of light, with a squared value of 0.241 $\pm$ 0.002 (stat) $\pm$ 0.016 (syst) in natural units. The effective medium temperature, estimated using the mean transverse momentum, is 219 $\pm$ 8 (syst) MeV. The measured squared speed of sound at this temperature aligns precisely with predictions from lattice quantum chromodynamic (QCD) calculations. This result provides a stringent constraint on the equation of state of the created medium and direct evidence for a deconfined QCD phase being attained in relativistic nuclear collisions

Test of lepton flavor universality in B± ⁣→ ⁣K±μ+μ− {\mathrm{B}^{\pm}} \!\to\! \mathrm{K^{\pm}}\mu^{+}\mu^{-} and B± ⁣→ ⁣K±e+e− {\mathrm{B}^{\pm}} \!\to\! \mathrm{K^{\pm}}\mathrm{e}^+\mathrm{e}^- decays in proton-proton collisions at s= \sqrt{s} = 13 TeV

A test of lepton flavor universality in ${\mathrm{B}^{\pm}} \!\to\! \mathrm{K^{\pm}}\mu^{+}\mu^{-}$ and ${\mathrm{B}^{\pm}} \!\to\! \mathrm{K^{\pm}}\mathrm{e}^+\mathrm{e}^-$ decays, as well as a measurement of differential and integrated branching fractions of a nonresonant ${\mathrm{B}^{\pm}} \!\to\! \mathrm{K^{\pm}}\mu^{+}\mu^{-}$ decay are presented. The analysis is made possible by a dedicated data set of proton-proton collisions at $\sqrt{s} =$ 13 TeV recorded in 2018, by the CMS experiment at the LHC, using a special high-rate data stream designed for collecting about 10 billion unbiased b hadron decays. The ratio of the branching fractions $\mathcal{B}({\mathrm{B}^{\pm}} \!\to\! \mathrm{K^{\pm}}\mu^{+}\mu^{-})$ to $\mathcal{B}({\mathrm{B}^{\pm}} \!\to\! \mathrm{K^{\pm}}\mathrm{e}^+\mathrm{e}^-)$ is determined from the measured double ratio $R(\mathrm{K})$ of these decays to the respective branching fractions of the ${\mathrm{B}^{\pm}} \!\to\! {\mathrm{J}/\psi} \mathrm{K^{\pm}}$ with ${\mathrm{J}/\psi} \!\to\!\mu^{+}\mu^{-}$ and $\mathrm{e}^+\mathrm{e}^-$ decays, which allow for significant cancellation of systematic uncertainties. The ratio $R(\mathrm{K})$ is measured in the range 1.1 $< q^2 <$ 6.0 GeV$^2$, where $q$ is the invariant mass of the lepton pair, and is found to be $R(\mathrm{K})=$ 0.78 $^{+0.47}_{-0.23}$, in agreement with the standard model expectation $R(\mathrm{K}) \approx$ 1. This measurement is limited by the statistical precision of the electron channel. The integrated branching fraction in the same $q^2$ range, $\mathcal{B}({\mathrm{B}^{\pm}} \!\to\! \mathrm{K^{\pm}}\mu^{+}\mu^{-}) =$ (12.42 $\pm$ 0.68) $\times$ 10$^{-8}$, is consistent with the present world-average value and has a comparable precision.A test of lepton flavor universality in B$^{\pm}$$\to$ K$^{\pm}\mu^+\mu^-$ and B$^{\pm}$$\to$ K$^{\pm}$e$^+$e$^-$ decays, as well as a measurement of differential and integrated branching fractions of a nonresonant B$^{\pm}$$\to$ K$^{\pm}\mu^+\mu^-$ decay are presented. The analysis is made possible by a dedicated data set of proton-proton collisions at $\sqrt{s}$ = 13 TeV recorded in 2018, by the CMS experiment at the LHC, using a special high-rate data stream designed for collecting about 10 billion unbiased b hadron decays. The ratio of the branching fractions $\mathcal{B}$(B$^{\pm}$$\to$ K$^{\pm}\mu^+\mu^-$) to $\mathcal{B}$(B$^{\pm}$$\to$ K$^{\pm}$e$^+$e$^-$) is determined from the measured double ratio $R$(K) of these decays to the respective branching fractions of the B$^\pm$$\to$ J/$\psi$K$^\pm$ with J/$\psi$$\to$$\mu^+\mu^-$ and e$^+$e$^-$ decays, which allow for significant cancellation of systematic uncertainties. The ratio $R$(K) is measured in the range 1.1 $\lt q^2 \lt$ 6.0 GeV$^2$, where $q$ is the invariant mass of the lepton pair, and is found to be $R$(K) = 0.78$^{+0.47}_{-0.23}$, in agreement with the standard model expectation $R$(K) $\approx$ 1. This measurement is limited by the statistical precision of the electron channel. The integrated branching fraction in the same $q^2$ range, $\mathcal{B}$(B$^{\pm}$$\to$ K$^{\pm}\mu^+\mu^-$) = (12.42 $\pm$ 0.68) $\times$ 10$^{-8}$, is consistent with the present world-average value and has a comparable precision

Searches for violation of Lorentz invariance in tt‾ \mathrm{t} \overline{\mathrm{t}} production using dilepton events in proton-proton collisions at s= \sqrt{s}= 13 TeV

A search for violation of Lorentz invariance in the production of top quark pairs ($\mathrm{t} \overline{\mathrm{t}}$) is presented. The measured normalized differential $\mathrm{t} \overline{\mathrm{t}}$ production cross section, as function of the sidereal time, is examined for potential modulations induced by Lorentz-invariance breaking operators in an effective field theory extension of the standard model (SM). The cross section is measured from collision events collected by the CMS detector at a center-of-mass-energy of 13 TeV, corresponding to an integrated luminosity of 77.8 fb$^{-1}$, and containing one electron and one muon. The results are found to be compatible with zero, in agreement with the SM, and are used to bound the Lorentz-violating couplings to be in ranges of 1-8 $\times$ 10$^{-3}$ at 68% confidence level. This is the first precision test of the isotropy in special relativity with top quarks at the LHC, restricting further the bounds on such couplings by up two orders of magnitude with respect to previous searches conducted at the Tevatron.A search for violation of Lorentz invariance in the production of top quark pairs ($\mathrm{t\bar{t}}$) is presented. The measured normalized differential $\mathrm{t\bar{t}}$ production cross section, as function of the sidereal time, is examined for potential modulations induced by Lorentz-invariance breaking operators in an effective field theory extension of the standard model (SM). The cross section is measured from collision events collected by the CMS detector at a center-of-mass-energy of 13 TeV, corresponding to an integrated luminosity of 77.8 fb$^{-1}$, and containing one electron and one muon. The results are found to be compatible with zero, in agreement with the SM, and are used to bound the Lorentz-violating couplings to be in ranges of 1 - 8 $\times$ 10$^{-3}$ at 68% confidence level. This is the first precision test of the isotropy in special relativity with top quarks at the LHC, restricting further the bounds on such couplings by up two orders of magnitude with respect to previous searches conducted at the Tevatron

Observation of the Ξb−\Xi^-_\mathrm{b}→\toψ\psi(2S)Ξ−\Xi^- decay and studies of the Ξb∗0\Xi_\mathrm{b}^{\ast{}0} baryon in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceThe first observation of the decay $\Xi^-_\mathrm{b}$$\to$$\psi$(2S)$\Xi^-$ and measurement of the branching ratio of $\Xi^-_\mathrm{b}$$\to$$\psi$(2S)$\Xi^-$ to $\Xi^-_\mathrm{b}$$\to$ J/$\psi$$\Xi^-$ are presented. The J/$\psi$ and $\psi$(2S) mesons are reconstructed using their dimuon decay modes. The results are based on proton-proton colliding beam data from the LHC collected by the CMS experiment at $\sqrt{s}$ = 13 TeV in 2016-2018, corresponding to an integrated luminosity of 140 fb$^{-1}$. The branching fraction ratio is measured to be $\mathcal{B}$($\Xi^-_\mathrm{b}$$\to$$\psi$(2S)$\Xi^-$)/$\mathcal{B}$($\Xi^-_\mathrm{b}$$\to$ J/$\psi$$\Xi^-$) = 0.84$^{+0.21}_{-0.19}$ (stat) $\pm$ 0.10 (syst) $\pm$ 0.02 ($\mathcal{B}$), where the last uncertainty comes from the uncertainties in the branching fractions of the charmonium states. New measurements of the $\Xi_\mathrm{b}^{\ast{}0}$ baryon mass and natural width are also presented, using the $\Xi_\mathrm{b}^-\pi^+$ final state, where the $\Xi^-_\mathrm{b}$ baryon is reconstructed through the decays J/$\psi \Xi^-$, $\psi$(2S)$\Xi^-$, J/$\psi \Lambda$K$^-$, and J/$\psi \Sigma^0$K$^-$. Finally, the fraction of the $\Xi^-_\mathrm{b}$ baryons produced from $\Xi_\mathrm{b}^{\ast{}0}$ decays is determined