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Vaccine elicitation of HIV broadly neutralizing antibodies from engineered B cells

Huang, Deli; Tran, Jenny Tuyet; Olson, Alex; Vollbrecht, Thomas; Tenuta, Mary; Guryleva, Mariia, V; Fuller, Roberta P.; Schiffner, Torben; Abadejos, Justin R.; Couvrette, Lauren; Blane, Tanya R.; Saye, Karen; Li, Wenjuan; Landais, Elise; Gonzalez-Martin, A

NATURE COMMUNICATIONS
2020
VL / 11 - BP / - EP /
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. 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.

AccesS level

Gold DOAJ, Green published

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