Vaccine elicitation of HIV broadly neutralizing antibodies from engineered B cells.
Vaccine elicitation of HIV broadly neutralizing antibodies from engineered B cells.
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DOI：
10.1038/s41467-020-19650-8
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发表时间：
2020-11-17
影响因子：
16.6
通讯作者：
Voss JE
中科院分区：
文献类型：
--
作者：
Huang D;Tran JT;Olson A;Vollbrecht T;Tenuta M;Guryleva MV;Fuller RP;Schiffner T;Abadejos JR;Couvrette L;Blane TR;Saye K;Li W;Landais E;Gonzalez-Martin A;Schief W;Murrell B;Burton DR;Nemazee D;Voss JE
HIV广泛中和抗体（bnAbs）具有抑制病毒血症和保护机体免受HIV感染的作用。然而，由于适当的前体B细胞受体的低频率和从这些前体产生bnAbs所需的复杂成熟途径，它们的激发变得困难。抗体基因既可以作为细胞表面的功能性抗原受体表达，也可以作为分泌抗体表达。本研究表明，HIV - bnAb工程原代小鼠B细胞可以过继性转移并接种于免疫能力小鼠，从而扩大持久的bnAb记忆和长寿的浆细胞。免疫后的体细胞超突变表明工程细胞有能力对不断进化的病原体作出反应。这些结果鼓励进一步探索工程化B细胞疫苗作为持久激发HIV抗体的策略，以防止感染，并作为功能性HIV治愈的一个因素。一种从工程B细胞中产生持久的HIV广泛中和抗体（bnAb）的疫苗有望成为HIV功能性治愈方法。在这里，作者展示了CRISPR/ cas修饰的表达bnAb作为功能性抗原受体的B细胞可以在小鼠中免疫产生长寿的生发中心成熟的bnAb记忆细胞和浆细胞。
HIV broadly neutralizing antibodies (bnAbs) can suppress viremia and protect against HIV infection. However, their elicitation is made difficult by low frequencies of appropriate precursor B cell receptors and the complex maturation pathways required to generate bnAbs from these precursors. Antibody genes can be engineered into B cells for expression as both a functional antigen receptor on cell surfaces and as secreted antibody. Here, we show that HIV bnAb-engineered primary mouse B cells can be adoptively transferred and vaccinated in immunocompetent mice resulting in the expansion of durable bnAb memory and long-lived plasma cells. Somatic hypermutation after immunization indicates that engineered cells have the capacity to respond to an evolving pathogen. These results encourage further exploration of engineered B cell vaccines as a strategy for durable elicitation of HIV bnAbs to protect against infection and as a contributor to a functional HIV cure. A vaccine to generate durable HIV broadly neutralizing antibodies (bnAb) from engineered B cells holds promise as an HIV functional cure. Here, the authors show that CRISPR/Cas-modified B cells expressing bnAbs as functional antigen receptors can be immunized to generate long-lived, germinal centre matured bnAb memory and plasma cells in mice.
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影响因子：
16.6
作者：
Nahmad AD;Raviv Y;Horovitz-Fried M;Sofer I;Akriv T;Nataf D;Dotan I;Carmi Y;Burstein D;Wine Y;Benhar I;Barzel A
通讯作者：
Barzel A
影响因子：
6.4
作者：
D'Souza, Lucas;Gupta, Sneh Lata;George, Anna
通讯作者：
George, Anna
FC修饰的HIV-1人单克隆抗体VRC01LS的安全性和药代动力学：健康成年人中的1期开放标签临床试验。
影响因子：
15.8
作者：
Gaudinski MR;Coates EE;Houser KV;Chen GL;Yamshchikov G;Saunders JG;Holman LA;Gordon I;Plummer S;Hendel CS;Conan-Cibotti M;Lorenzo MG;Sitar S;Carlton K;Laurencot C;Bailer RT;Narpala S;McDermott AB;Namboodiri AM;Pandey JP;Schwartz RM;Hu Z;Koup RA;Capparelli E;Graham BS;Mascola JR;Ledgerwood JE;VRC 606 Study Team
通讯作者：
VRC 606 Study Team
影响因子：
14.9
作者：
Brinkman EK;Chen T;Amendola M;van Steensel B
通讯作者：
van Steensel B
影响因子：
14.9
作者：
Kumar, Venkatesh;Vollbrecht, Thomas;Murrell, Ben
通讯作者：
Murrell, Ben