92 research outputs found
Understanding Sentinel-1 Backscatter Response to Sugarcane Yield Variability and Waterlogging
Sentinel-1 observes the whole globe every 12 days (6 days when both satellites were operational) and provides a wealth of data relevant to agriculture. Sugarcane cultivators could potentially benefit from these data by using them to assist operational and management practices. However, first, thorough understanding is needed of Sentinel-1 backscatter and its behavior over sugarcane canopies. In this study, we aimed to improve understanding of how Sentinel-1 backscatter responds to sugarcane yield variability and waterlogging. In order to do so we focused on an irrigated sugarcane plantation in Xinavane, Mozambique. In the analysis presented, we assessed different polarizations, their ratio, and benchmarked them against optical indices and passive microwave observations in different seasons. With the help of a large sugarcane yield dataset, we analyzed how backscatter relates to sucrose yield variability in different seasons. We found VV backscatter related to the stalk development, the most important reservoir for sucrose accumulation. In addition, in a season with reported waterlogging, optical and radar observations showed a delay in sugarcane crop development. Further analysis showed the presence of water underneath the canopy caused an increase in all polarizations and the cross ratio (CR). The results imply that Sentinel-1 backscatter contains information on both waterlogging under the canopy as well as sucrose development in the stalk. By isolating and quantifying the impact of waterlogging on backscatter, it will be possible to further quantify sucrose development with backscatter observations and identify waterlogging simultaneously.Peer reviewe
Improving the immunogenicity of native-like HIV-1 envelope trimers by hyperstabilization
The production of native-like recombinant versions of the HIV-1 envelope glycoprotein (Env) trimer requires overcoming the natural flexibility and instability of the complex. The engineered BG505 SOSIP.664 trimer mimics the structure and antigenicity of native Env. Here, we describe how the introduction of new disulfide bonds between the glycoprotein (gp)120 and gp41 subunits of SOSIP trimers of the BG505 and other genotypes improves their stability and antigenicity, reduces their conformational flexibility, and helps maintain them in the unliganded conformation. The resulting next-generation SOSIP.v5 trimers induce strong autologous tier-2 neutralizing antibody (NAb) responses in rabbits. In addition, the BG505 SOSIP.v6 trimers induced weak heterologous NAb responses against a subset of tier-2 viruses that were not elicited by the prototype BG505 SOSIP.664. These stabilization methods can be applied to trimers from multiple genotypes as components of multivalent vaccines aimed at inducing broadly NAbs (bNAbs)
Structural conservation of Lassa virus glycoproteins and recognition by neutralizing antibodies
Lassa fever is an acute hemorrhagic fever caused by the zoonotic Lassa virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and is the sole target for neutralizing antibodies. Immunogen design is complicated by the metastable nature of recombinant GPCs and the antigenic differences among phylogenetically distinct LASV lineages. Despite the sequence diversity of the GPC, structures of most lineages are lacking. We present the development and characterization of prefusion-stabilized, trimeric GPCs of LASV lineages II, V, and VII, revealing structural conservation despite sequence diversity. High-resolution structures and biophysical characterization of the GPC in complex with GP1-A-specific antibodies suggest their neutralization mechanisms. Finally, we present the isolation and characterization of a trimer-preferring neutralizing antibody belonging to the GPC-B competition group with an epitope that spans adjacent protomers and includes the fusion peptide. Our work provides molecular detail information on LASV antigenic diversity and will guide efforts to design pan-LASV vaccines
Bispecific antibodies combine breadth, potency, and avidity of parental antibodies to neutralize sarbecoviruses
SARS-CoV-2 variants evade current monoclonal antibody therapies. Bispecific antibodies (bsAbs) combine the specificities of two distinct antibodies taking advantage of the avidity and synergy provided by targeting different epitopes. Here we used controlled Fab-arm exchange to produce bsAbs that neutralize SARS-CoV and SARS-CoV-2 variants, including Omicron and its subvariants, by combining potent SARS-CoV-2-specific neutralizing antibodies with broader antibodies that also neutralize SARS-CoV. We demonstrated that the parental antibodies rely on avidity for neutralization using bsAbs containing one irrelevant Fab arm. Using mass photometry to measure the formation of antibody:spike complexes, we determined that bsAbs increase binding stoichiometry compared to corresponding cocktails, without a loss of binding affinity. The heterogeneous binding pattern of bsAbs to spike, observed by negative-stain electron microscopy and mass photometry provided evidence for both intra- and inter-spike crosslinking. This study highlights the utility of cross-neutralizing antibodies for designing bivalent agents to combat circulating and future SARS-like coronaviruses
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