Engineered B cells expressing an anti-HIV antibody enable memory retention, isotype switching and clonal expansion

Alessio D. Nahmad, Yuval Raviv, Miriam Horovitz-Fried, Ilan Sofer, Tal Akriv, Daniel Nataf, Iris Dotan, Yaron Carmi, David Burstein, Yariv Wine, Itai Benhar, Adi Barzel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

HIV viremia can be controlled by chronic antiretroviral therapy. As a potentially single-shot alternative, B cells engineered by CRISPR/Cas9 to express anti-HIV broadly neutralizing antibodies (bNAbs) are capable of secreting high antibody titers. Here, we show that, upon immunization of mice, adoptively transferred engineered B cells home to germinal centers (GC) where they predominate over the endogenous response and differentiate into memory and plasma cells while undergoing class switch recombination (CSR). Immunization with a high affinity antigen increases accumulation in GCs and CSR rates. Boost immunization increases the rate of engineered B cells in GCs and antibody secretion, indicating memory retention. Finally, antibody sequences of engineered B cells in the spleen show patterns of clonal selection. Therefore, B cells can be engineered into what could be a living and evolving drug.

Original languageEnglish
Article number5851
JournalNature Communications
Volume11
Issue number1
DOIs
StatePublished - Dec 2020

Funding

FundersFunder number
Horizon 2020 Framework Programme759296
Israel Science Foundation1692/18, 2157/16, 1632/16
theH2020 European Research Council

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