Badger, C. V. | Search bioRxiv

bioRxiv2021

LY-CoV1404 potently neutralizes SARS-CoV-2 variants

SARS-CoV-2 neutralizing monoclonal antibodies (mAbs) can reduce the risk of hospitalization when administered early during COVID-19 disease. However, the emergence of variants of concern has negatively impacted the therapeutic use of some authorized mAbs. Using a high throughput B-cell screening pipeline, we isolated a highly potent SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody called LY-CoV1404 (also known as bebtelovimab). LY-CoV1404 potently neutralizes authentic SARS-CoV-2 virus, including the prototype, B.1.1.7, B.1.351 and B.1.617.2). In pseudovirus neutralization studies, LY-CoV1404 retains potent neutralizing activity against numerous variants including B.1.1.7, B.1.351, B.1.617.2, B.1.427/B.1.429, P.1, B.1.526, B.1.1.529, and the BA.2 subvariant and retains binding to spike proteins with a variety of underlying RBD mutations including K417N, L452R, E484K, and N501Y. Structural analysis reveals that the contact residues of the LY-CoV1404 epitope are highly conserved with the exception of N439 and N501. Notably, the binding and neutralizing activity of LY-CoV1404 is unaffected by the most common mutations at these positions (N439K and N501Y). The breadth of reactivity to amino acid substitutions present among current VOC together with broad and potent neutralizing activity and the relatively conserved epitope suggest that LY-CoV1404 has the potential to be an effective therapeutic agent to treat all known variants causing COVID-19. In BriefLY-CoV1404 is a potent SARS-CoV-2-binding antibody that neutralizes all known variants of concern and whose epitope is rarely mutated. HighlightsO_LILY-CoV1404 potently neutralizes SARS-CoV-2 authentic virus and known variants of concern including the B.1.1.529 (Omicron), the BA.2 Omicron subvariant, and B.1.617.2 (Delta) variants C_LIO_LINo loss of potency against currently circulating variants C_LIO_LIBinding epitope on RBD of SARS-CoV-2 is rarely mutated in GISAID database C_LIO_LIBreadth of neutralizing activity and potency supports clinical development C_LI

immunology↗

bioRxiv2018

Virus-Like Particles and Magnetic Microspheres Provide a Flexible and Sustainable Multiplexed Alphavirus Immunodiagnostic Platform

There is a pressing need for sustainable and sensitive immunodiagnostics for use in public health efforts to understand and combat the threat of endemic and emerging infectious diseases. We describe a novel approach to immunodiagnostics based on virus-like particles (VLPs) attached to magnetic beads. This flexible, innovative immunoassay system, based on the MAGPIX(R) platform, improves sensitivity by up to 2-logs and has faster sample-to-answer time over traditional methods. As a proof of concept, a retroviral-based VLP, that presents the Venezuelan equine encephalitis virus E1/E2 glycoprotein antigen on its surface, was generated and coupled to magnetic beads to create VLP-conjugated microspheres (VCMs). Using these VCMs, IgG and IgM antibodies were detectable in nonhuman primate (NHP) and human clinical serum samples at dilutions of 1 x 104 and greater. We extended the VCM methodology to two other New-World alphaviruses, eastern and western equine encephalitis viruses, as well as an Old-World alphavirus, Chikungunya virus, demonstrating the flexibility of this approach toward different VLP architectures. When multiplexed on the MAGPIX(R) platform, the VCMs provided differential diagnosis between Old-World and New-World alphaviruses and well as a route toward assessing the humoral response to both natural infection and vaccination. This VCM system will allow more rapid and efficient detection of endemic and emerging viral pathogens in human populations.

microbiology↗