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Search: WFRF:(McInerney GM)

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  • Custodio, TF, et al. (author)
  • Selection, biophysical and structural analysis of synthetic nanobodies that effectively neutralize SARS-CoV-2
  • 2020
  • In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 5588-
  • Journal article (peer-reviewed)abstract
    • The coronavirus SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Therapeutic neutralizing antibodies constitute a key short-to-medium term approach to tackle COVID-19. However, traditional antibody production is hampered by long development times and costly production. Here, we report the rapid isolation and characterization of nanobodies from a synthetic library, known as sybodies (Sb), that target the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Several binders with low nanomolar affinities and efficient neutralization activity were identified of which Sb23 displayed high affinity and neutralized pseudovirus with an IC50 of 0.6 µg/ml. A cryo-EM structure of the spike bound to Sb23 showed that Sb23 binds competitively in the ACE2 binding site. Furthermore, the cryo-EM reconstruction revealed an unusual conformation of the spike where two RBDs are in the ‘up’ ACE2-binding conformation. The combined approach represents an alternative, fast workflow to select binders with neutralizing activity against newly emerging viruses.
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  • Forsell, MNE, et al. (author)
  • Increased human immunodeficiency virus type 1 Env expression and antibody induction using an enhanced alphavirus vector
  • 2007
  • In: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 88:Pt 10, s. 2774-2779
  • Journal article (peer-reviewed)abstract
    • Viral vectors encoding heterologous vaccine antigens are potent inducers of cellular immune responses, but they are generally less efficient at stimulating humoral immunity. To improve the induction of antibody responses by Semliki Forest virus-based vaccines, a vector encoding a translation-enhancer element and a novel internal signal sequence for increased expression and secretion of soluble antigens was designed. Approximately tenfold more human immunodeficiency virus type 1 gp120 was secreted into culture supernatants of infected cells using the enhanced vector compared with the parental vector. This translated into a significant increase in gp120-specific antibodies in immunized mice, suggesting that antigen-expression levels from the parental vector are limiting for induction of antibody responses. These data encourage the use of the enhanced vector for elicitation of immune responses against heterologous antigens during vaccination.
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