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Monoclonal antibodies directed against trimeric forms of the HIV-1 envelope glycoprotein with broad and potent neutralizing activity

机译:针对具有广泛而有效的中和活性的HIV-1包膜糖蛋白三聚体形式的单克隆抗体

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 are 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.
机译:本发明提供了一种获得广泛中和抗体(bNab)的方法,包括从供体PBMC样品中筛选记忆B细胞培养物对多种HIV-1种类的中和活性,克隆表现出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。所得单克隆抗体的特征在于它们能够以天然或单体形式选择性结合来自Env蛋白的表位,以及抑制来自多个进化枝的HIV-1物种的感染的能力。提供了用于预防,诊断和治疗HIV感染的含有人单克隆抗HIV抗体的组合物。提供了通过使用来自gp120可变环内的保守区域的表位免疫而产生这种抗体的方法。还提供了用于产生抗HIV1 bNAb的免疫原。此外,提供了使用合适的表位进行疫苗接种的方法。

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