Protection and mechanism of action of a novel human respiratory syncytial virus vaccine candidate based on the extracellular domain of small hydrophobic protein

Infections with human respiratory syncytial virus (HRSV) occur globally in all age groups and can have devastating consequences in young infants. We demonstrate that a vaccine based on the extracellular domain (SHe) of the small hydrophobic (SH) protein of HRSV, reduced viral replication in challenged laboratory mice and in cotton rats. We show that this suppression of viral replication can be transferred by serum and depends on a functional IgG receptor compartment with a major contribution of FcRI and FcRIII. Using a conditional cell depletion method, we provide evidence that alveolar macrophages are involved in the protection by SHe-specific antibodies. HRSV-infected cells abundantly express SH on the cell surface and are likely the prime target of the humoral immune response elicited by SHe-based vaccination. Finally, natural infection of humans and experimental infection of mice or cotton rats does not induce a strong immune response against HRSV SHe. Using SHe as a vaccine antigen induces immune protection against HRSV by a mechanism that differs from the natural immune response and from other HRSV vaccination strategies explored to date. Hence, HRSV vaccine candidates that aim at inducing protective neutralizing antibodies or T-cell responses could be complemented with a SHe-based antigen to further improve immune protection

Energy Momentum Pseudo-Tensor of Relic Gravitational Wave in Expanding Universe

We study the energy-momentum pseudo-tensor of gravitational wave, and examine the one introduced by Landau-Lifshitz for a general gravitational field and the effective one recently used in literature. In short wavelength limit after Brill-Hartle average, both lead to the same gauge invariant stress tensor of gravitational wave. For relic gravitational waves in the expanding universe, we examine two forms of pressure, $p_{gw}$ and $\mathcal{P}_{gw}$, and trace the origin of their difference to a coupling between gravitational waves and the background matter. The difference is shown to be negligibly small for most of cosmic expansion stages starting from inflation. We demonstrate that the wave equation is equivalent to the energy conservation equation using the pressure $\mathcal{P}_{gw}$ that includes the mentioned coupling.Comment: 15 pages, no figure, Accepted by PR

The retention of S35-labelled bovine serum albumin on normal and immunized rabbit liver tissue

The S35-label of S35-BSA was detected in the liver tissue of rabbits to the extent of 0.02 per cent (10 µg or sime 1014 molecules) of the injected material at 140 days after injection. The rate of loss of antigen at the termination of the experiment was of such an order that significant amounts would be expected to persist for at least several years. Data are reported which extend the retention data previously reported on S35-labelled hemocyanin. They indicate that amounts of the order of 0.05 per cent (25 µg.) of antigen material persist at 330 days after injection. All of the radioactivity of material retained in the liver tissue 6 weeks after injection was immunologically related to the original S35-BSA antigen. Preliminary studies are reported which indicate that the retained antigen is bound to ribonucleic acid. A new method is described for the isolation of p-azophenylsulfonate bovine serum albumin from tissue extracts by means of a Dowex 2 adsorbent

The effect of abrupt weaning of suckler calves on the plasma concentrations of cortisol, catecholamines, leukocyte, acute-phase proteins and in vitro interferon-gamma production

End of project reportThe objective of this study was to examine the effect of abrupt weaning (inclusive of social group disruption and maternal separation) on the physiological mediators of stress and measures of immune function. Thirty-eight male and 38 female continental calves were habituated to handling for two weeks prior to bleeding. Calves were blocked on sex, weight and breed of dam and randomly assigned, within block, to either a control (cows remain with calves) or abruptly weaned group (calves removed from cows). Animals were separated into the respective treatment groups at weaning (0 h). Calves were bled at – 168 h, 6 h (males only), 24 h, 48 h and 168 h post weaning. At each sampling time an observer scored the behavioural reaction of calves to sampling. Blood samples were analysed for cortisol, catecholamine concentrations (not sampled at –168 h) and in vitro interferon-gamma production, neutrophil :lymphocyte ratio and acute phase protein concentrations. All continuous data were analysed using a split-plot ANOVA, except that collected at 6 h, which was analysed using a single factor ANOVA model. The effects of weaning, calf sex and time and respective interactions were described. Disruption of the established social groups at 0 h, increased (p<0.001) the plasma cortisol concentration and neutrophil: lymphocyte ratio and reduced the leukocyte concentration (p<0.001) and the in vitro interferon-gamma response to the mitogen concanavalin-A (p<0.001) and keyhole limpet haemocyanin (p<0.001) for weaned and control animals, when compared with –168h. Plasma adrenaline and noradrenaline concentrations were not affected by group disruption. There was no effect of weaning or sex on calf behavioural reaction to handling during blood sampling. Plasma cortisol and adrenaline concentrations were not affected by weaning or sex. Plasma noradrenaline concentration was influenced by weaning x sex (p<0.05) and time x sex (p<0.05). The response increased for male calves with weaning and increased with each sampling time post weaning. For heifers the response was not affected by weaning and plasma concentrations decreased at 168 h post weaning. There was no effect of weaning or sex on leukocyte concentration. The neutrophils : lymphocyte ration increased post weaning (p<0.01) and was affected by sex (p<0.05). Weaning decreased (p<0.05) the in vitro interferon-gamma response to the antigen KLH. There was a time x weaning x sex (p<0.05) interaction for fibrinogen concentration but no effect of treatment on haptoglobin concentration. Abrupt weaning increased plasma cortisol and nor-adrenaline concentrations, which was accompanied by attenuation of in vitro interferon gamma production to novel mitogen and antigen complexes up to 7 days post weaning.European Union Structural Funds (EAGGF

Competition of haptens

Groups of rabbits were injected with either bovine serum albumin, sheep red cell stroma, or keyhole limpet hemocyanin to which 2,4-dinitrophenyl and/or p-azophenyl arsonate groups had been coupled. Groups of animals received either doubly coupled antigen or an equivalent mixture of singly coupled antigens. Materials were injected intravenously as a solution or subcutaneously and intramuscularly in complete Freund's adjuvant. The presence of dinitrophenyl groups on the immunizing antigen could suppress, partially or completely, the antibody response to p-azophenyl arsonate when this hapten was located on the same molecule. Suppression was dependent on the ratio of haptenic groups on the molecule, appeared to be greatly affected by the method of immunization, and could be demonstrated in all three antigen systems. Partial suppression was manifested in decreased frequency and delayed appearance of the response as well as decreased maximal antibody titers. These findings appear irreconcilable with the possibility of direct clonal selection of antibody-producing cells by unprocessed antigen

Tuning thermoelectric power factor by crystal-field and spin-orbit couplings in Kondo lattice materials

We study thermoelectric transport at low temperatures in correlated Kondo insulators, motivated by the recent observation of a high thermoelectric figure of merit(ZT) in $FeSb_2$ at $T \sim 10 K$. Even at room temperature, correlations have the potential to lead to high ZT, as in $YbAl_3$, one of the most widely used thermoelectric metals. At low temperature correlation effects are especially worthy of study because fixed band structures are unlikely to give rise to the very small energy gaps $E_g \sim 5 kT$ necessary for a weakly correlated material to function efficiently at low temperature. We explore the possibility of improving the thermoelectric properties of correlated Kondo insulators through tuning of crystal field and spin-orbit coupling and present a framework to design more efficient low-temperature thermoelectrics based on our results.Comment: 8 pages, 9 figure

Severe B Cell Deficiency in Mice Lacking the Tec Kinase Family Members Tec and Btk

The cytoplasmic protein tyrosine kinase Tec has been proposed to have important functions in hematopoiesis and lymphocyte signal transduction. Here we show that Tec-deficient mice developed normally and had no major phenotypic alterations of the immune system. To reveal potential compensatory roles of other Tec kinases such as Bruton's tyrosine kinase (Btk), Tec/Btk double-deficient mice were generated. These mice exhibited a block at the B220+CD43+ stage of B cell development and displayed a severe reduction of peripheral B cell numbers, particularly immunoglobulin (Ig)MloIgDhi B cells. Although Tec/Btknull mice were able to form germinal centers, the response to T cell–dependent antigens was impaired. Thus, Tec and Btk together have an important role both during B cell development and in the generation and/or function of the peripheral B cell pool. The ability of Tec to compensate for Btk may also explain phenotypic differences in X-linked immunodeficiency (xid) mice compared with human X-linked agammaglobulinemia (XLA) patients

Soft Expansion of Double-Real-Virtual Corrections to Higgs Production at N3^3LO

We present methods to compute higher orders in the threshold expansion for the one-loop production of a Higgs boson in association with two partons at hadron colliders. This process contributes to the N$^3$LO Higgs production cross section beyond the soft-virtual approximation. We use reverse unitarity to expand the phase-space integrals in the small kinematic parameters and to reduce the coefficients of the expansion to a small set of master integrals. We describe two methods for the calculation of the master integrals. The first was introduced for the calculation of the soft triple-real radiation relevant to N$^3$LO Higgs production. The second uses a particular factorization of the three body phase-space measure and the knowledge of the scaling properties of the integral itself. Our result is presented as a Laurent expansion in the dimensional regulator, although some of the master integrals are computed to all orders in this parameter.Comment: 30 page