公开(公告)号：EP2926830B1

公开(公告)日：2017-08-02

申请号：EP14004015.5

申请日：2011-08-31

申请人： Theraclone Sciences, Inc. ,  The Scripps Research Institute ,  International Aids Vaccine Initiative

发明人： CHAN-HUI, Po-Ying ,  DOORES, Katherine ,  HUBER, Michael ,  KAMINSKY, Stephen ,  FREY, Steven ,  OLSEN, Ole ,  MITCHAM, Jennifer ,  MOYLE, Matthew ,  PHOGAT, Sanjay K. ,  BURTON, Dennis R. ,  WALKER, Laura Marjorie ,  POIGNARD, Pascal Raymond Georges ,  KOFF, Wayne ,  SIMEK-LEMOS, Melissa Danielle ...

IPC分类号： A61K39/00 ,  A61K39/21 ,  C07K16/10

CPC分类号： C07K16/1063 ,  A61K39/21 ,  A61K2039/505 ,  C07K16/1045 ,  C07K2317/21 ,  C07K2317/33 ,  C07K2317/34 ,  C07K2317/51 ,  C07K2317/515 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92

摘要： The invention provides a method for obtaining a broadly neutralizing antibody (bNab), including screening memory B cell cultures from a donor PBMC sample for neutralization activity against a plurality of HIV-1 species, cloning a memory B cell that exhibits broad neutralization activity; and rescuing a monoclonal antibody from that memory B cell culture. The resultant monoclonal antibodies may be characterized by their ability to selectively bind epitopes from the Env proteins in native or monomeric form, as well as to inhibit infection of HIV-1 species from a plurality of clades. Compositions containing human monoclonal anti-HIV antibodies used for prophylaxis, diagnosis and treatment of HIV infection are provided. Methods for generating such antibodies by immunization using epitopes from conserved regions within the variable loops of gp120 are provided. Immunogens for generating anti-HIV1 bNAbs are also provided. Furthermore, methods for vaccination using suitable epitopes are provided.

摘要翻译： 本发明提供了获得广泛中和抗体（bNab）的方法，包括筛选来自供体PBMC样品的记忆B细胞培养物的针对多种HIV-1物种的中和活性，克隆展现广泛中和活性的记忆B细胞; 并从该记忆B细胞培养物中拯救单克隆抗体。 得到的单克隆抗体的特征可在于其以天然或单体形式选择性结合Env蛋白的表位的能力，以及抑制来自多个进化枝的HIV-1物种的感染。 提供了含有用于预防，诊断和治疗HIV感染的人单克隆抗HIV抗体的组合物。 提供了使用来自gp120的可变环内的保守区的表位进行免疫来产生此类抗体的方法。 还提供了用于产生抗HIV1bNAb的免疫原。 此外，提供了使用合适表位的疫苗接种方法。