Publications by authors named "L Varani"
Unlocking the potential of broadly reactive coronavirus monoclonal antibodies (mAbs) and their derivatives offers a transformative therapeutic avenue against severe COVID-19, especially crucial for safeguarding high-risk populations. Novel mAb-based immunotherapies may help address the reduced efficacy of current vaccines and neutralizing mAbs caused by the emergence of variants of concern (VOCs). Using phage display technology, we discovered a pan-SARS-CoV-2 mAb (C10) that targets a conserved region within the receptor-binding domain (RBD) of the virus.
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- Flaviviruses like dengue, Zika, and yellow fever are transmitted by mosquitoes and cause diseases primarily in tropical regions, while Powassan virus (POWV) is tick-borne and found in temperate areas.
- Research shows that people in Mexico and Brazil have neutralizing antibodies against POWV, suggesting possible exposure to the virus.
- Monoclonal antibodies P002 and P003 target a shared epitope on POWV, hinting that POWV or a similar virus could infect humans in tropical locations.
Article Synopsis
- The emergence of Omicron subvariants challenges the effectiveness of current vaccines and therapeutic antibodies, leading to increased breakthrough infections linked to weak mucosal IgA responses from mRNA vaccines.
- Researchers engineered new forms of IgA antibodies that showed significantly improved neutralizing abilities against various Omicron lineages compared to traditional IgG antibodies.
- Administering these enhanced IgA antibodies nasally could offer a promising strategy for both preventing and treating Omicron infections, addressing issues of immune evasion by newer variants.
Analytical ultracentrifugation (AUC) analysis shows that the SARS-CoV-2 trimeric Spike (S) protein adopts different quaternary conformations in solution. The relative abundance of the "open" and "close" conformations is temperature-dependent, and samples with different storage temperature history have different open/close distributions. Neutralizing antibodies (NAbs) targeting the S receptor binding domain (RBD) do not alter the conformer populations; by contrast, a NAb targeting a cryptic conformational epitope skews the Spike trimer toward an open conformation.
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