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Affinity maturation endows potent activity onto class 6 SARS-CoV-2 broadly neutralizing antibodies.
Proc Natl Acad Sci U S A
January 2025
Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
The emergence of SARS-CoV-2 variants of concern (VOCs) has greatly diminished the neutralizing activity of previously FDA-approved monoclonal antibodies (mAbs), including that of antibody cocktails and of first-generation broadly neutralizing antibodies such as S309 (Sotrovimab). In contrast, antibodies targeting cryptic conformational epitopes of the receptor binding domain (RBD) have demonstrated broad activity against emerging variants, but exert only moderate neutralizing activity, which has so far hindered clinical development. Here, we utilize in vitro display technology to identify and affinity-mature antibodies targeting the cryptic class 6 epitope, accessible only in the "up" conformation of the SARS-CoV-2 spike trimer.
View Article and Find Full Text PDFEngineering mRNA vaccine with broad-spectrum protection against SARS-cov-2 variants.
Biochem Biophys Res Commun
December 2024
Nanjing Shenxin Biotechnology Co., Ltd., 211800, China. Electronic address:
Herd immunity through mass vaccination is an effective method for preventing infectious diseases. However, the emerging SARS-CoV-2 variants, with their frequent mutations, largely evade the immune response and protection induced by COVID-19 vaccines. Here, we designed messenger RNAs encoding mutant epitopes of the spike protein shared among various COVID-19 variants.
View Article and Find Full Text PDFVaccination with different group 2 influenza subtypes alters epitope targeting and breadth of hemagglutinin stem-specific human B cells.
Sci Transl Med
January 2025
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20902, USA.
The conserved influenza hemagglutinin stem, which is a target of cross-neutralizing antibodies, is now used in vaccine strategies focused on protecting against influenza pandemics. Antibody responses to group 1 stem have been extensively characterized, but little is known about group 2. Here, we characterized the stem-specific repertoire of individuals vaccinated with one of three group 2 influenza subtypes (H3, H7, or H10).
View Article and Find Full Text PDFStructural Immunology of SARS-CoV-2.
Immunol Rev
December 2024
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
The SARS-CoV-2 spike (S) protein has undergone significant evolution, enhancing both receptor binding and immune evasion. In this review, we summarize ongoing efforts to develop antibodies targeting various epitopes of the S protein, focusing on their neutralization potency, breadth, and escape mechanisms. Antibodies targeting the receptor-binding site (RBS) typically exhibit high neutralizing potency but are frequently evaded by mutations in SARS-CoV-2 variants.
View Article and Find Full Text PDFEnhanced Antibody Response to the Conformational Non-RBD Region DNA Prime-Protein Boost Elicits Broad Cross-Neutralization Against SARS-CoV-2 Variants.
Emerg Microbes Infect
December 2024
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan 650000, China.
Preventing immune escape of SARS-CoV-2 variants is crucial in vaccine development to ensure broad protection against the virus. Conformational epitopes beyond the RBD region are vital components of the spike protein but have received limited attention in the development of broadly protective SARS-CoV-2 vaccines. In this study, we used a DNA prime-protein boost regimen to evaluate the broad cross-neutralization potential of immune response targeting conformational non-RBD region against SARS-CoV-2 viruses in mice.
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