Vaccine elicitation of HIV broadly neutralizing antibodies from engineered B cells

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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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Huang, D., Tran, J. T., Olson, A., Vollbrecht, T., Tenuta, M., Guryleva, M. V., … Voss, J. E. (2020). Vaccine elicitation of HIV broadly neutralizing antibodies from engineered B cells. Nature Communications, 11(1). https://doi.org/10.1038/s41467-020-19650-8

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