| Autor: |
Lutje Hulsik D; Unit of Virus Host Cell Interactions (UVHCI), UMI 3265, Université Joseph Fourier-EMBL-CNRS, Grenoble, France., Liu YY, Strokappe NM, Battella S, El Khattabi M, McCoy LE, Sabin C, Hinz A, Hock M, Macheboeuf P, Bonvin AM, Langedijk JP, Davis D, Forsman Quigley A, Aasa-Chapman MM, Seaman MS, Ramos A, Poignard P, Favier A, Simorre JP, Weiss RA, Verrips CT, Weissenhorn W, Rutten L |
| Jazyk: |
angličtina |
| Zdroj: |
PLoS pathogens [PLoS Pathog] 2013 Mar; Vol. 9 (3), pp. e1003202. Date of Electronic Publication: 2013 Mar 07. |
| DOI: |
10.1371/journal.ppat.1003202 |
| Abstrakt: |
The membrane proximal external region (MPER) of the HIV-1 glycoprotein gp41 is targeted by the broadly neutralizing antibodies 2F5 and 4E10. To date, no immunization regimen in animals or humans has produced HIV-1 neutralizing MPER-specific antibodies. We immunized llamas with gp41-MPER proteoliposomes and selected a MPER-specific single chain antibody (VHH), 2H10, whose epitope overlaps with that of mAb 2F5. Bi-2H10, a bivalent form of 2H10, which displayed an approximately 20-fold increased affinity compared to the monovalent 2H10, neutralized various sensitive and resistant HIV-1 strains, as well as SHIV strains in TZM-bl cells. X-ray and NMR analyses combined with mutagenesis and modeling revealed that 2H10 recognizes its gp41 epitope in a helical conformation. Notably, tryptophan 100 at the tip of the long CDR3 is not required for gp41 interaction but essential for neutralization. Thus bi-2H10 is an anti-MPER antibody generated by immunization that requires hydrophobic CDR3 determinants in addition to epitope recognition for neutralization similar to the mode of neutralization employed by mAbs 2F5 and 4E10. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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