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 Fuller, Torben Schiffner, Justin R. Abadejos, Lauren Couvrette, Tanya R. Blane, Karen Saye, Wenjuan Li, Elise Landais, Alicia González-Martín, William R. 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.