Induction of potent neutralizing antibody responses by a designed protein nanoparticle accine for respiratory syncytial virus

Respiratory syncytial virus (RSV) is a worldwide public health concern for which no vaccine is available. Elucidation of the prefusion structure of the RSV F glycoprotein and its identification as the main target of neutralizing antibodies have provided new opportunities for development of an effective vaccine. Here, we describe the structure-based design of a self-assembling protein nanoparticle presenting a prefusion-stabilized variant of the F glycoprotein trimer (DS-Cav1) in a repetitive array on the nanoparticle exterior. The two-component nature of the nanoparticle scaffold enabled the production of highly ordered, monodisperse immunogens that display DS-Cav1 at controllable density. In mice and nonhuman primates, the full-valency nanoparticle immunogen displaying 20 DS-Cav1 trimers induced neutralizing antibody responses ∼10-fold higher than trimeric DS-Cav1. These results motivate continued development of this promising nanoparticle RSV vaccine candidate and establish computationally designed two-component nanoparticles as a robust and customizable platform for structure-based vaccine design

Physiological, biochemical, and ultrastructural characterization of selenium toxicity in cowpea plants

Selenium (Se) is considered a beneficial element for plants; however, in high concentrations, it causes negative effects on plant physiology and development. This study reports the first physiological, nutritional, and ultrastructural description of Se toxicity in cowpea growing under field conditions. Selenium was supplied as a foliar application of sodium selenite at varying concentrations (0, 50, 100, 200, 400, 800, 1200, and 1600 g ha−1). An increased yield was observed with the application of 50 g ha−1 Se. Application of concentrations higher than 50 g ha−1 caused leaf toxicity. Increased lipid peroxidation and hydrogen peroxide concentration and reduced total sugars, sucrose, and carotenoid concentration were observed at highest doses tested (1200 and 1600 g ha−1). Applications of more than 50 g ha−1 Se reduced the phloem diameter, caused chlorosis of the leaf blade with a coalescence of lesions, and caused pink salt deposits to appear. Lesions were observed mainly near the trichomes on the adaxial surface of the leaf blade. An analysis of the element distribution with microprobe X-ray fluorescence spectrometry (μ-XRF) revealed accumulation of Se, calcium (Ca), potassium (K), copper (Cu), and manganese (Mn) near the primary vein and in the necrotic brown areas of the leaf lesions. In contrast, Na was homogeneously distributed in the leaf tissue

Rationally designed Human Cytomegalovirus gB nanoparticle vaccine with improved immunogenicity.

Human cytomegalovirus (HCMV) is the primary viral cause of congenital birth defects and causes significant morbidity and mortality in immune-suppressed transplant recipients. Despite considerable efforts in vaccine development, HCMV infection still represents an unmet clinical need. In recent phase II trials, a MF59-adjuvanted gB vaccine showed only modest efficacy in preventing infection. These findings might be attributed to low level of antibodies (Abs) with a neutralizing activity induced by this vaccine. Here, we analyzed the immunogenicity of each gB antigenic domain (AD) and demonstrated that domain I of gB (AD5) is the main target of HCMV neutralizing antibodies. Furthermore, we designed, characterized and evaluated immunogenic responses to two different nanoparticles displaying a trimeric AD5 antigen. We showed that mice immunization with nanoparticles induces sera neutralization titers up to 100-fold higher compared to those obtained with the gB extracellular domain (gBECD). Collectively, these results illustrate with a medically relevant example the advantages of using a general approach combining antigen discovery, protein engineering and scaffold presentation for modern development of subunit vaccines against complex pathogens

Laboratory data in support of JWST observations of interstellar ices

Laboratory astrophysics and astrochemistr

Platelet-derived growth factor-α receptor is the cellular receptor for human cytomegalovirus gHgLgO trimer

Human cytomegalovirus encodes at least 25 membrane glycoproteins that are found in the viral envelope1. While gB represents the fusion protein, two glycoprotein complexes control the tropism of the virus: the gHgLgO trimer is involved in the infection of fibroblasts, and the gHgLpUL128L pentamer is required for infection of endothelial, epithelial and myeloid cells 2-5. Two reports suggested that gB binds to ErbB1 and PDGFR\u3b1 (refs 6,7); however, these results do not explain the tropism of the virus and were recently challenged 8,9. Here, we provide a 19\ue2 \u20ac...\uc5 reconstruction for the gHgLgO trimer and show that it binds with high affinity through the gO subunit to PDGFR\u3b1, which is expressed on fibroblasts but not on epithelial cells. We also provide evidence that the trimer is essential for viral entry in both fibroblasts and epithelial cells. Furthermore, we identify the pentamer, which is essential for infection of epithelial cells, as a trigger for the ErbB pathway. These findings help explain the broad tropism of human cytomegalovirus and indicate that PDGFR\u3b1 and the viral gO subunit could be targeted by novel anti-viral therapies