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

Research output: Contribution to journalArticlepeer-review

36 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 - 17 Nov 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2020, The Author(s).

Funding

We thank the Veterinary Service Center, Tel Aviv University for animal husbandry and the IDRFU and SICF units, Tel Aviv university for logistic support. We also thank Omri Wurtzel, Ziv Shulman, Natalia Freund, Steffen Jung, Adi Stern, Limor Nahary, Ariel Munitz, Avishay Dolitzsky, Israel Zan-Bar, Yaron Hillman, Almog Bitton, Hila Kobo, Ludovic Deriano, Rina Rosin-Arbesfeld and Natalie Zelikson for reagents and feedback. This research was funded by theH2020 European Research Council grant 759296 (A.B.) and the Israel Science Foundation grants: 1632/16 (A.B), 2157/16 (A.B.), 1692/18 (D.B.).

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

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