Engaging an HIV vaccine target through the acquisition of low B cell affinity.
Engaging an HIV vaccine target through the acquisition of low B cell affinity.
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DOI：
10.1038/s41467-023-40918-2
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发表时间：
2023-08-28
影响因子：
16.6
通讯作者：
Lingwood D
中科院分区：
文献类型：
--
作者：
Ronsard L;Yousif AS;Nait Mohamed FA;Feldman J;Okonkwo V;McCarthy C;Schnabel J;Caradonna T;Barnes RM;Rohrer D;Lonberg N;Schmidt A;Lingwood D
低亲和力对于种系B细胞受体（BCR）接种开发广泛中和抗体（bnAb）是常见的，所述广泛中和抗体（bnAb）接合高变病毒（包括HIV）。抗体亲和性选择也是非选择性的，确保了低亲和性B细胞克隆的存活。为了探索这是否为针对保守疫苗靶标扩增人B细胞谱系提供了一个天然窗口，我们部署了模拟人抗体多样性和体细胞超突变（SHM）的转基因小鼠，并用简单的单体HIV糖蛋白包膜免疫原免疫。我们报告了一种免疫方案，通过常规亲和力成熟和可重复扩增SHM中具有公共模式的低亲和力BCR克隆，将B细胞记忆集中在保守的CD4结合位点（CD4bs）上。在后一种情况下，SHM通过降低结合强度来促进靶向获取。这表明允许的B细胞选择使得能够发现抗体表位，在这种情况下是HIV bnAb位点。HIV的广泛中和抗体（bnAb）一直难以引发，其中一个问题是所需的低B细胞亲和力。在这里，作者使用携带人样抗体库的转基因小鼠来显示低亲和力B细胞持续存在，这使得针对CD4结合位点（一种保守的HIV bnAb靶标）的抗体的疫苗扩增成为可能。
Low affinity is common for germline B cell receptors (BCR) seeding development of broadly neutralizing antibodies (bnAbs) that engage hypervariable viruses, including HIV. Antibody affinity selection is also non-homogenizing, insuring the survival of low affinity B cell clones. To explore whether this provides a natural window for expanding human B cell lineages against conserved vaccine targets, we deploy transgenic mice mimicking human antibody diversity and somatic hypermutation (SHM) and immunize with simple monomeric HIV glycoprotein envelope immunogens. We report an immunization regimen that focuses B cell memory upon the conserved CD4 binding site (CD4bs) through both conventional affinity maturation and reproducible expansion of low affinity BCR clones with public patterns in SHM. In the latter instance, SHM facilitates target acquisition by decreasing binding strength. This suggests that permissive B cell selection enables the discovery of antibody epitopes, in this case an HIV bnAb site. Broadly neutralizing antibodies (bnAbs) for HIV have been difficult to elicit with one issue being the low B cell affinity required. Here the authors use a transgenic mouse bearing human-like antibody repertoires to show that low affinity B cells persist which enables vaccine expansion of antibodies against the CD4 binding site, a conserved HIV bnAb target.
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影响因子：
14.3
作者：
Caniels, Tom G.;Medina-Ramirez, Max;Zhang, Jinsong;Sarkar, Anita;Kumar, Sonu;LaBranche, Alex;Derking, Ronald;Allen, Joel D.;Snitselaar, Jonne L.;Capella-Pujol, Joan;Sanchez, Ivan del Moral;Yasmeen, Anila;Diaz, Marilyn;Aldon, Yoann;Bijl, Tom P. L.;Venkatayogi, Sravani;Beem, Joshua S. Martin;Newman, Amanda;Jiang, Chuancang;Lee, Wen-Hsin;Pater, Maarten;Burger, Judith A.;Breemen, Marielle J. van;Taeye, Steven W. de;Rantalainen, Kimmo;LaBranche, Celia;Saunders, Kevin O.;Montefiori, David;Ozorowski, Gabriel;Ward, Andrew B.;Crispin, Max;Moore, John P.;Klasse, Per Johan;Haynes, Barton F.;Wilson, Ian A.;Wiehe, Kevin;Verkoczy, Laurent;Sanders, Rogier W.
通讯作者：
Sanders, Rogier W.
影响因子：
64.5
作者：
Briney, Bryan;Sok, Devin;Jardine, Joseph G.;Kulp, Daniel W.;Skog, Patrick;Menis, Sergey;Jacak, Ronald;Kalyuzhniy, Oleksandr;de Val, Natalia;Sesterhenn, Fabian;Le, Khoa M.;Ramos, Alejandra;Jones, Meaghan;Saye-Francisco, Karen L.;Blane, Tanya R.;Spencer, Skye;Georgeson, Erik;Hu, Xiaozhen;Ozorowski, Gabriel;Adachi, Yumiko;Kubitz, Michael;Sarkar, Anita;Wilson, Ian A.;Ward, Andrew B.;Nemazee, David;Burton, Dennis R.;Schief, William R.
通讯作者：
Schief, William R.
定义和操纵B细胞免疫优势层次结构，以广泛中和针对流感病毒的抗体反应。
影响因子：
9.3
作者：
Amitai A;Sangesland M;Barnes RM;Rohrer D;Lonberg N;Lingwood D;Chakraborty AK
通讯作者：
Chakraborty AK
DOI：
10.1038/s41577-022-00753-w
发表时间：
2023-03
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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影响因子：
15.3
作者：
Dosenovic, Pia;Pettersson, Anna-Klara;McGuire, Andrew T.
通讯作者：
McGuire, Andrew T.