Vaccine Elicitation of HIV Broadly Neutralizing Antibodies from Engineered B cells
Jenny Tuyet Tran,
Mariia V Guryleva,
Roberta P Fuller,
Justin R Abadejos,
Tanya R. Blane,
Dennis R. Burton,
James E. Voss
Posted 17 Mar 2020
bioRxiv DOI: 10.1101/2020.03.17.989699
Posted 17 Mar 2020
HIV broadly neutralizing antibodies (bnAbs) can suppress viremia and protect against 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 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 wild-type animals resulting in the expansion of durable bnAb memory and long-lived plasma cells. Somatic hypermutation after immunization indicated 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 cure.
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