Author:
Huang Deli,Tran Jenny Tuyet,Olson Alex,Vollbrecht Thomas,Guryleva Mariia V.,Tenuta Mary,Fuller Roberta P.,Schiffner Torben,Abadejos Justin R.,Couvrette Lauren,Blane Tanya R.,Saye Karen,Li Wenjuan,Landais Elise,Gonzalez-Martin Alicia,Schief William,Murrell Ben,Burton Dennis R.,Nemazee David,Voss James E.
Abstract
HIV broadly neutralizing antibodies (bnAbs) can suppress viremia and protect against infection1. 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 precursors2. Antibody genes can be engineered into B cells for expression as both a functional receptor on cell surfaces and as secreted antibody3–5. 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.
Publisher
Cold Spring Harbor Laboratory
Cited by
3 articles.
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