Vaccine elicitation of HIV broadly neutralizing antibodies from engineered B cells

疫苗诱导基因工程改造的B细胞产生广谱HIV中和抗体

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作者:Deli Huang ,Jenny Tuyet Tran ,Alex Olson ,Thomas Vollbrecht ,Mary Tenuta ,Mariia V Guryleva ,Roberta P Fuller ,Torben Schiffner ,Justin R Abadejos ,Lauren Couvrette ,Tanya R Blane ,Karen Saye ,Wenjuan Li ,Elise Landais ,Alicia Gonzalez-Martin ,William Schief ,Ben Murrell ,Dennis R Burton ,David Nemazee ,James E Voss

Abstract

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.

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