Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Department of Medicine, The University of California San Diego, La Jolla, CA, USA.
Nat Commun. 2020 Nov 17;11(1):5850. doi: 10.1038/s41467-020-19650-8.
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.
HIV 广谱中和抗体(bnAbs)可以抑制病毒血症并预防 HIV 感染。然而,由于合适的前体 B 细胞受体频率较低,以及从这些前体产生 bnAbs 所需的复杂成熟途径,其诱导变得困难。抗体基因可以被工程改造到 B 细胞中,作为功能性抗原受体在细胞表面表达,并作为分泌型抗体。在这里,我们表明,HIV bnAb 工程化的原代小鼠 B 细胞可以被过继转移并在免疫功能正常的小鼠中接种,从而导致持久的 bnAb 记忆和长寿浆细胞的扩增。免疫后的体细胞超突变表明,工程化细胞有能力对不断进化的病原体做出反应。这些结果鼓励进一步探索工程化 B 细胞疫苗作为一种持久诱导 HIV bnAbs 的策略,以预防感染,并作为功能性 HIV 治愈的贡献者。