RSV disease in infants and young children: Can we see a brighter future?

Respiratory syncytial virus (RSV) is a highly contagious seasonal virus and the leading cause of Lower Respiratory Tract Infections (LRTI), including pneumonia and bronchiolitis in children. RSV-related LRTI cause approximately 3 million hospitalizations and 120,000 deaths annually among children <5 years of age. The majority of the burden of RSV occurs in previously healthy infants. Only a monoclonal antibody (mAb) has been approved against RSV infections in a restricted group, leaving an urgent unmet need for a large number of children potentially benefiting from preventive measures. Approaches under development include maternal vaccines to protect newborns, extended half-life monoclonal antibodies to provide rapid long-lasting protection, and pediatric vaccines. RSV has been identified as a major global priority but a solution to tackle this unmet need for all children has yet to be implemented. New technologies represent the avenue for effectively addressing the leading-cause of hospitalization in children <1 years old

MRI as a Novel In Vivo Approach for Assessing Structural Changes of Chlamydia Pathology in a Mouse Model.

Chlamydia trachomatis is among the most prevalent of sexually transmitted diseases. While Chlamydia infection is a reportable event and screening has increased over time, enhanced surveillance has not resulted in a reduction in the rate of infections, and Chlamydia infections frequently recur. The development of a preventative vaccine for Chlamydia may be the only effective approach for reducing infection and the frequency of pathological outcomes. Current vaccine research efforts involve time consuming and/or invasive approaches for assessment of disease state, and MRI presents a clinically translatable method for assessing infection and related pathology both quickly and non-invasively. Longitudinal T2-weighted MRI was performed over 63 days on both control or Chlamydia muridarum challenged mice, either with or without elementary body (EB) immunization, and gross necropsy was performed on day 65. A scoring system was developed to assess the number of regions affected by Chlamydia pathology and was used to document pathology over time and at necropsy. The scoring system documented increasing incidence of pathology in the unimmunized and challenged mice (significantly greater compared to the control and EB immunized-challenged groups) by 21 days post-challenge. No differences between the unchallenged and EB immunized-challenged mice were observed. MRI scores at Day 63 were consistently higher than gross necropsy scores at Day 65, although two of the three groups of mice showed no significant differences between the two techniques. In this work we describe the application of MRI in mice for the potential evaluation of disease pathology and sequelae caused by C. muridarum infection and this technique's potential for evaluation of vaccines for Chlamydia

Preclinical optimization of an enterotoxigenic Escherichia coli adjuvanted subunit vaccine using response surface design of experiments

International audienceEnterotoxigenic E. coli (ETEC) is a leading cause of moderate-to-severe diarrhoea. ETEC colonizes the intestine through fimbrial tip adhesin colonization factors and produces heat-stable and/or heat-labile (LT) toxins, stimulating fluid and electrolyte release leading to watery diarrhoea. We reported that a vaccine containing recombinant colonization factor antigen (CfaEB) targeting fimbrial tip adhesin of the colonization factor antigen I (CFA/I) and an attenuated LT toxoid (dmLT) elicited mucosal and systemic immune responses against both targets. Additionally, the toll-like receptor 4 ligand second-generation lipid adjuvant (TLR4-SLA) induced a potent mucosal response, dependent on adjuvant formulation. However, a combination of vaccine components at their respective individual optimal doses may not achieve the optimal immune profile. We studied a subunit ETEC vaccine prototype in mice using a response surface design of experiments (DoE), consisting of 64 vaccine dose-combinations of CfaEB, dmLT and SLA in four formulations (aqueous, aluminium oxyhydroxide, squalene-in-water stable nanoemulsion [SE] or liposomes containing the saponin Quillaja saponaria-21 [LSQ]). Nine readouts focusing on antibody functionality and plasma cell response were selected to profile the immune response of parenterally administered ETEC vaccine prototype. The data were integrated in a model to identify the optimal dosage of each vaccine component and best formulation. Compared to maximal doses used in mouse models (10 µg CfaEB, 1 µg dmLT and 5 µg SLA), a reduction in the vaccine components up to 37%, 60% and 88% for CfaEB, dmLT and SLA, respectively, maintained or even maximized immune responses, with SE and LSQ the best formulations. The DoE approach can help determine the best vaccine composition with a limited number of experiments and may accelerate development of multi-antigen/ component ETEC vaccines

Impact of Surface Roughness on AMSR-E Sea Ice Products

This paper examines the sensitivity of Advanced Microwave Scanning Radiometer (AMSR-E) brightness temperatures (Tbs) to surface roughness by a using radiative transfer model to simulate AMSR-E Tbs as a function of incidence angle at which the surface is viewed. The simulated Tbs are then used to examine the influence that surface roughness has on two operational sea ice algorithms, namely: 1) the National Aeronautics and Space Administration Team (NT) algorithm and 2) the enhanced NT algorithm, as well as the impact of roughness on the AMSR-E snow depth algorithm. Surface snow and ice data collected during the AMSR-Ice03 field campaign held in March 2003 near Barrow, AK, were used to force the radiative transfer model, and resultant modeled Tbs are compared with airborne passive microwave observations from the Polarimetric Scanning Radiometer. Results indicate that passive microwave Tbs are very sensitive even to small variations in incidence angle, which can cause either an over or underestimation of the true amount of sea ice in the pixel area viewed. For example, this paper showed that if the sea ice areas modeled in this paper mere assumed to be completely smooth, sea ice concentrations were underestimated by nearly 14% using the NT sea ice algorithm and by 7% using the enhanced NT algorithm. A comparison of polarization ratios (PRs) at 10.7,18.7, and 37 GHz indicates that each channel responds to different degrees of surface roughness and suggests that the PR at 10.7 GHz can be useful for identifying locations of heavily ridged or rubbled ice. Using the PR at 10.7 GHz to derive an "effective" viewing angle, which is used as a proxy for surface roughness, resulted in more accurate retrievals of sea ice concentration for both algorithms. The AMSR-E snow depth algorithm was found to be extremely sensitive to instrument calibration and sensor viewing angle, and it is concluded that more work is needed to investigate the sensitivity of the gradient ratio at 37 and 18.7 GHz to these factors to improve snow depth retrievals from spaceborne passive microwave sensors

Incidence of Positive Pathology in Ovaries/Oviducts Detected by MRI Images.

<p>Incidence of Positive Pathology in Ovaries/Oviducts Detected by MRI Images.</p

Bacterial counts recovered by vaginal swab.

<p>Summary of the course of infection over the first three weeks after challenge, as measured by qPCR.</p