Vaccine elicitation of HIV broadly neutralizing antibodies from engineered B cells

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 () and James E. Voss ()
Additional contact information
Deli Huang: The Scripps Research Institute
Jenny Tuyet Tran: The Scripps Research Institute
Alex Olson: The Scripps Research Institute
Thomas Vollbrecht: The University of California San Diego
Mary Tenuta: The Scripps Research Institute
Mariia V. Guryleva: Tumor and Cell Biology, Karolinska Institutet
Roberta P. Fuller: The Scripps Research Institute
Torben Schiffner: The Scripps Research Institute
Justin R. Abadejos: The Scripps Research Institute
Lauren Couvrette: The Scripps Research Institute
Tanya R. Blane: The Scripps Research Institute
Karen Saye: The Scripps Research Institute
Wenjuan Li: The Scripps Research Institute
Elise Landais: The Scripps Research Institute
Alicia Gonzalez-Martin: Universidad Autónoma de Madrid (UAM) and Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM)
William Schief: The Scripps Research Institute
Ben Murrell: Tumor and Cell Biology, Karolinska Institutet
Dennis R. Burton: The Scripps Research Institute
David Nemazee: The Scripps Research Institute
James E. Voss: The Scripps Research Institute

Nature Communications, 2020, vol. 11, issue 1, 1-10

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-19650-8

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