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TitleDevelopmental pathway for potent V1V2-directed HIV-neutralizing antibodies.
Journal, issue, pagesNature, Vol. 509, Issue 7498, Page 55-62, Year 2014
Publish dateMay 1, 2014
AuthorsNicole A Doria-Rose / Chaim A Schramm / Jason Gorman / Penny L Moore / Jinal N Bhiman / Brandon J DeKosky / Michael J Ernandes / Ivelin S Georgiev / Helen J Kim / Marie Pancera / Ryan P Staupe / Han R Altae-Tran / Robert T Bailer / Ema T Crooks / Albert Cupo / Aliaksandr Druz / Nigel J Garrett / Kam H Hoi / Rui Kong / Mark K Louder / Nancy S Longo / Krisha McKee / Molati Nonyane / Sijy O'Dell / Ryan S Roark / Rebecca S Rudicell / Stephen D Schmidt / Daniel J Sheward / Cinque Soto / Constantinos Kurt Wibmer / Yongping Yang / Zhenhai Zhang / / James C Mullikin / James M Binley / Rogier W Sanders / Ian A Wilson / John P Moore / Andrew B Ward / George Georgiou / Carolyn Williamson / Salim S Abdool Karim / Lynn Morris / Peter D Kwong / Lawrence Shapiro / John R Mascola /
PubMed AbstractAntibodies capable of neutralizing HIV-1 often target variable regions 1 and 2 (V1V2) of the HIV-1 envelope, but the mechanism of their elicitation has been unclear. Here we define the developmental ...Antibodies capable of neutralizing HIV-1 often target variable regions 1 and 2 (V1V2) of the HIV-1 envelope, but the mechanism of their elicitation has been unclear. Here we define the developmental pathway by which such antibodies are generated and acquire the requisite molecular characteristics for neutralization. Twelve somatically related neutralizing antibodies (CAP256-VRC26.01-12) were isolated from donor CAP256 (from the Centre for the AIDS Programme of Research in South Africa (CAPRISA)); each antibody contained the protruding tyrosine-sulphated, anionic antigen-binding loop (complementarity-determining region (CDR) H3) characteristic of this category of antibodies. Their unmutated ancestor emerged between weeks 30-38 post-infection with a 35-residue CDR H3, and neutralized the virus that superinfected this individual 15 weeks after initial infection. Improved neutralization breadth and potency occurred by week 59 with modest affinity maturation, and was preceded by extensive diversification of the virus population. HIV-1 V1V2-directed neutralizing antibodies can thus develop relatively rapidly through initial selection of B cells with a long CDR H3, and limited subsequent somatic hypermutation. These data provide important insights relevant to HIV-1 vaccine development.
External linksNature / PubMed:24590074 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.895 - 28.0 Å
Structure data

EMDB-5856:
Negative stain reconstruction of HIV envelope glycoprotein BG505 SOSIP.664 in complex with CAP256-VRC26.09 Fab
Method: EM (single particle) / Resolution: 28.0 Å

PDB-4ocr:
Crystal structure of human Fab CAP256-VRC26.01, a potent V1V2-directed HIV-1 neutralizing antibody
Method: X-RAY DIFFRACTION / Resolution: 1.895 Å

PDB-4ocs:
Crystal structure of human Fab CAP256-VRC26.10, a potent V1V2-directed HIV-1 neutralizing antibody
Method: X-RAY DIFFRACTION / Resolution: 1.901 Å

PDB-4ocw:
Crystal structure of human Fab CAP256-VRC26.06, a potent V1V2-directed HIV-1 neutralizing antibody
Method: X-RAY DIFFRACTION / Resolution: 3.001 Å

PDB-4od1:
Crystal structure of human Fab CAP256-VRC26.03, a potent V1V2-directed HIV-1 neutralizing antibody
Method: X-RAY DIFFRACTION / Resolution: 2.69 Å

PDB-4od3:
Crystal structure of human Fab CAP256-VRC26.07, a potent V1V2-directed HIV-1 neutralizing antibody
Method: X-RAY DIFFRACTION / Resolution: 2.616 Å

PDB-4odh:
Crystal structure of human Fab CAP256-VRC26.UCA, a potent V1V2-directed HIV-1 neutralizing antibody
Method: X-RAY DIFFRACTION / Resolution: 2.894 Å

PDB-4org:
Crystal structure of human Fab CAP256-VRC26.04, a potent V1V2-directed HIV-1 neutralizing antibody
Method: X-RAY DIFFRACTION / Resolution: 3.121 Å

Chemicals

ChemComp-HOH:
WATER

ChemComp-ZN:
Unknown entry

ChemComp-MES:
2-(N-MORPHOLINO)-ETHANESULFONIC ACID / pH buffer*YM

Source
  • Human immunodeficiency virus 1
  • homo sapiens (human)
KeywordsIMMUNE SYSTEM / Fab / HIV-1 / V1V2 / CAP256 / VRC26

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