公开(公告)号：EP2895500A4

公开(公告)日：2016-04-13

申请号：EP13837551

申请日：2013-09-12

申请人： UNIV DUKE ,  LOS ALAMOS NAT SECURITY LLC ,  UNIV PENNSYLVANIA ,  UNIV BOSTON ,  US GOV HEALTH & HUMAN SERV ,  UNIV LELAND STANFORD JUNIOR

发明人： HAYNES BARTON F ,  LIAO HUA-XIN ,  LYNCH REBECCA M ,  ZHOU TONGQING ,  GAO FENG ,  BOYD SCOTT ,  SHAW GEORGE M ,  HAHN BEATRICE H ,  KEPLER THOMAS B ,  KORBER BETTE T ,  KWONG PETER ,  MASCOLA JOHN

IPC分类号： C07K14/155 ,  A61K39/12 ,  A61P31/18

CPC分类号： A61K39/21 ,  A61K39/12 ,  A61K2039/57 ,  C07K14/005 ,  C12N7/00 ,  C12N2740/15022 ,  C12N2740/16022 ,  C12N2740/16122 ,  C12N2740/16134

摘要： The present invention relates, in general, to HIV-1 and, in particular, to broadly neutralizing HIV-1 antibodies, and to HIV-1 immunogens and to methods of using such immunogens to induce the production of broadly neutralizing HIV-1 antibodies in a subject (e.g., a human).

公开(公告)号：EP2707388A4

公开(公告)日：2014-12-31

申请号：EP12782672

申请日：2012-03-23

申请人： UNIV DUKE ,  US GOVERNMENT

发明人： MASCOLA JOHN R ,  NABEL GARY ,  HAYNES BARTON F ,  WU XUELING ,  KEPLER THOMAS B ,  KWONG PETER

IPC分类号： C07K16/10 ,  A61K39/42 ,  A61P31/18 ,  C12N15/13

CPC分类号： C07K16/1063 ,  C07K2317/21 ,  C07K2317/565 ,  C07K2317/76 ,  G01N33/56988

摘要： Antibody VRC01 represents a human immunoglobulin that neutralizes—˜90% of diverse HIV-1 isolates. To understand how such broadly neutralizing HIV-1 antibodies develop and recognize the viral envelope, we used X-ray crystallography and 454 pyrosequencing to characterize additional antibodies from HIV-1-infected individuals. Crystal structures revealed a convergent mode of binding of different antibodies to the same CD4-binding-site epitope. Antibody recognition was achieved through the evolution of complementary contact domains that were generated in diverse ways. Phylogenetic analysis of expressed heavy and light chains determined by deep sequencing revealed a common pathway of antibody heavy chain maturation confined to IGHV1-2*02 lineage that could pair with different light chains. The maturation pathway inferred by antibodyomics reveals that diverse antibodies evolve to a highly affinity-matured state to recognize an invariant viral structure, providing insight into the development and evolution of broadly neutralizing HIV-1 immunity.