Matches in SemOpenAlex for { <https://semopenalex.org/work/W2007202358> ?p ?o ?g. }
- W2007202358 endingPage "183" @default.
- W2007202358 startingPage "170" @default.
- W2007202358 abstract "Following CD4 receptor binding to the HIV-1 envelope spike (Env), the conserved N-heptad repeat (NHR) region of gp41 forms a coiled-coil that is a precursor to the fusion reaction. Although it has been a target of drug and vaccine design, there are few monoclonal antibody (mAb) tools with which to probe the antigenicity and immunogenicity specifically of the NHR coiled-coil. Here, we have rescued HIV-1-neutralizing anti-NHR mAbs from immune phage display libraries that were prepared (i) from b9 rabbits immunized with a previously described mimetic of the NHR coiled-coil, N35(CCG)-N13, and (ii) from an HIV-1 infected individual. We describe a rabbit single-chain Fv fragment (scFv), 8K8, and a human Fab, DN9, which specifically recognize NHR coiled-coils that are unoccupied by peptide corresponding to the C-heptad repeat or CHR region of gp41 (e.g. C34). The epitopes of 8K8 and DN9 were found to partially overlap with that of a previously described anti-NHR mAb, IgG D5; however, 8K8 and DN9 were much more specific than D5 for unoccupied NHR trimers. The mAbs, including a whole IgG 8K8 molecule, neutralized primary HIV-1 of clades B and C in a pseudotyped virus assay with comparable, albeit relatively modest potency. Finally, a human Fab T3 and a rabbit serum (both non-neutralizing) were able to block binding of D5 and 8K8 to a gp41 NHR mimetic, respectively, but not the neutralizing activity of these mAbs. We conclude from these results that NHR coiled-coil analogs of HIV-1 gp41 elicit many Abs during natural infection and through immunization, but that due to limited accessibility to the corresponding region on fusogenic gp41 few can neutralize. Caution is therefore required in targeting the NHR for vaccine design. Nevertheless, the mAb panel may be useful as tools for elucidating access restrictions to the NHR of gp41 and in designing potential improvements to mimetics of receptor-activated Env." @default.
- W2007202358 created "2016-06-24" @default.
- W2007202358 creator A5020335387 @default.
- W2007202358 creator A5021246410 @default.
- W2007202358 creator A5024727980 @default.
- W2007202358 creator A5024978070 @default.
- W2007202358 creator A5043527143 @default.
- W2007202358 creator A5044275994 @default.
- W2007202358 creator A5048026726 @default.
- W2007202358 creator A5053779953 @default.
- W2007202358 creator A5055747549 @default.
- W2007202358 creator A5058546353 @default.
- W2007202358 creator A5073322790 @default.
- W2007202358 creator A5074112300 @default.
- W2007202358 creator A5075936228 @default.
- W2007202358 creator A5080807667 @default.
- W2007202358 creator A5088670445 @default.
- W2007202358 creator A5091606860 @default.
- W2007202358 date "2008-07-01" @default.
- W2007202358 modified "2023-09-29" @default.
- W2007202358 title "Antibody elicited against the gp41 N-heptad repeat (NHR) coiled-coil can neutralize HIV-1 with modest potency but non-neutralizing antibodies also bind to NHR mimetics" @default.
- W2007202358 cites W1490369813 @default.
- W2007202358 cites W1495740329 @default.
- W2007202358 cites W1607434342 @default.
- W2007202358 cites W1627654352 @default.
- W2007202358 cites W1635348995 @default.
- W2007202358 cites W1664573657 @default.
- W2007202358 cites W1794879226 @default.
- W2007202358 cites W1909984710 @default.
- W2007202358 cites W1947238875 @default.
- W2007202358 cites W1969552295 @default.
- W2007202358 cites W1970818121 @default.
- W2007202358 cites W1973581581 @default.
- W2007202358 cites W1973844352 @default.
- W2007202358 cites W1974729150 @default.
- W2007202358 cites W1976244486 @default.
- W2007202358 cites W1977389533 @default.
- W2007202358 cites W1985932590 @default.
- W2007202358 cites W1990407513 @default.
- W2007202358 cites W1990971245 @default.
- W2007202358 cites W1991112092 @default.
- W2007202358 cites W1995355944 @default.
- W2007202358 cites W2001383387 @default.
- W2007202358 cites W2005780220 @default.
- W2007202358 cites W2008606951 @default.
- W2007202358 cites W2013399404 @default.
- W2007202358 cites W2020333667 @default.
- W2007202358 cites W2020857934 @default.
- W2007202358 cites W2022712848 @default.
- W2007202358 cites W2023162377 @default.
- W2007202358 cites W2023434411 @default.
- W2007202358 cites W2023768779 @default.
- W2007202358 cites W2024977015 @default.
- W2007202358 cites W2026215931 @default.
- W2007202358 cites W2030648131 @default.
- W2007202358 cites W2031637541 @default.
- W2007202358 cites W2032211300 @default.
- W2007202358 cites W2033669661 @default.
- W2007202358 cites W2036441104 @default.
- W2007202358 cites W2036656105 @default.
- W2007202358 cites W2038063067 @default.
- W2007202358 cites W2040684562 @default.
- W2007202358 cites W2041675911 @default.
- W2007202358 cites W2042437669 @default.
- W2007202358 cites W2046427690 @default.
- W2007202358 cites W2048336729 @default.
- W2007202358 cites W2051804158 @default.
- W2007202358 cites W2053336940 @default.
- W2007202358 cites W2057503542 @default.
- W2007202358 cites W2059056215 @default.
- W2007202358 cites W2059445854 @default.
- W2007202358 cites W2063701397 @default.
- W2007202358 cites W2065081325 @default.
- W2007202358 cites W2069981708 @default.
- W2007202358 cites W2072278974 @default.
- W2007202358 cites W2072901265 @default.
- W2007202358 cites W2075009216 @default.
- W2007202358 cites W2076991562 @default.
- W2007202358 cites W2080089116 @default.
- W2007202358 cites W2080508669 @default.
- W2007202358 cites W2083391421 @default.
- W2007202358 cites W2083956673 @default.
- W2007202358 cites W2086841541 @default.
- W2007202358 cites W2090763940 @default.
- W2007202358 cites W2096950500 @default.
- W2007202358 cites W2097594050 @default.
- W2007202358 cites W2099308199 @default.
- W2007202358 cites W2102548388 @default.
- W2007202358 cites W2106197125 @default.
- W2007202358 cites W2107316250 @default.
- W2007202358 cites W2111105264 @default.
- W2007202358 cites W2111491631 @default.
- W2007202358 cites W2117948751 @default.
- W2007202358 cites W2118820599 @default.
- W2007202358 cites W2119680349 @default.
- W2007202358 cites W2122710825 @default.
- W2007202358 cites W2124935744 @default.
- W2007202358 cites W2126817706 @default.