一种由疫苗诱导产生的 CD4 结合位点牛抗体对 HIV-1 的广谱和超强中和作用。
Broad and ultra-potent cross-clade neutralization of HIV-1 by a vaccine-induced CD4 binding site bovine antibody.
机构信息
Department of Microbiology and Immunology, The Peter Doherty Institute for Infection Immunity, University of Melbourne, Melbourne, VIC 3000, Australia.
Department of Surgery, Duke University Medical Center, Durham, NC, USA.
出版信息
Cell Rep Med. 2022 May 17;3(5):100635. doi: 10.1016/j.xcrm.2022.100635.
Human immunodeficiency virus type 1 (HIV-1) vaccination of cows has elicited broadly neutralizing antibodies (bNAbs). In this study, monoclonal antibodies (mAbs) are isolated from a clade A (KNH1144 and BG505) vaccinated cow using a heterologous clade B antigen (AD8). CD4 binding site (CD4bs) bNAb (MEL-1872) is more potent than a majority of CD4bs bNAbs isolated so far. MEL-1872 mAb with CDRH3 of 57 amino acids shows more potency (geometric mean half-maximal inhibitory concentration [IC]: 0.009 μg/mL; breadth: 66%) than VRC01 against clade B viruses (29-fold) and than CHO1-31 against tested clade A viruses (21-fold). It also shows more breadth and potency than NC-Cow1, the only other reported anti-HIV-1 bovine bNAb, which has 60% breadth with geometric mean IC of 0.090 μg/mL in this study. Using successive different stable-structured SOSIP trimers in bovines can elicit bNAbs focusing on epitopes ubiquitous across subtypes. Furthermore, the cross-clade selection strategy also results in ultra-potent bNAbs.
人类免疫缺陷病毒 1 型（HIV-1）对奶牛的疫苗接种可引起广泛中和抗体（bnAbs）。在这项研究中，使用异源 clade B 抗原（AD8）从接种 clade A（KNH1144 和 BG505）的奶牛中分离出单克隆抗体（mAb）。CD4 结合位点（CD4bs）bnAb（MEL-1872）比迄今为止分离出的大多数 CD4bs bnAbs 更有效。具有 57 个氨基酸的 CDRH3 的 MEL-1872 mAb 显示出更强的效力（几何平均半最大抑制浓度[IC]：0.009μg/mL；广度：66％），对 clade B 病毒（29 倍）的 VRC01 和对测试的 clade A 病毒（21 倍）的 CHO1-31。与仅有的另一种报道的抗 HIV-1 牛 bnAb（NC-Cow1）相比，它还具有更广泛的广度和效力，该抗体在本研究中的广度为 60％，几何平均 IC 为 0.090μg/mL。在牛中使用连续的不同稳定结构 SOSIP 三聚体可以引发针对普遍存在于所有亚型中的表位的 bnAbs。此外，跨 clade 选择策略也会导致超有效 bnAbs。
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