Engineering pan–HIV-1 neutralization potency through multispecific antibody avidity-Reference-Cited by-同舟云学术

Engineering pan–HIV-1 neutralization potency through multispecific antibody avidity

Published:2022-01-21 Issue:4 Volume:119 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Rujas Edurne¹²³⁴^ORCID,Cui Hong¹,Burnie Jonathan⁵⁶,Aschner Clare Burn¹,Zhao Tiantian⁷,Insausti Sara³⁴^ORCID,Muthuraman Krithika¹²,Semesi Anthony¹,Ophel Jasper⁸^ORCID,Nieva Jose L.³⁴,Seaman Michael S.⁸^ORCID,Guzzo Christina⁵⁶^ORCID,Treanor Bebhinn⁵⁶⁷^ORCID,Julien Jean-Philippe¹²⁷^ORCID

Affiliation:

1. Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON M5G 0A4, Canada

2. Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada

3. Instituto Biofisika (UPV/EHU, CSIC), University of the Basque Country, Leioa 48940 , Spain

4. Department of Biochemistry and Molecular Biology, University of the Basque Country, Bilbao 48080, Spain

5. Department of Biological Sciences, University of Toronto Scarborough, Toronto, ON M1C 1A4, Canada

6. Department of Cell and Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada

7. Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada

8. Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215

Abstract

SignificanceThe high genetic diversity of HIV-1 continues to be a major barrier to the development of therapeutics for prevention and treatment. Here, we describe the design of an antibody platform that allows assembly of a highly avid, multispecific molecule that targets, simultaneously, the most conserved epitopes on the HIV-1 envelope glycoprotein. The combined multivalency and multispecificity translates into extraordinary neutralization potency and pan-neutralization of HIV-1 strains, surpassing that of the most potent anti-HIV broadly neutralizing antibody cocktails.

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Link

https://pnas.org/doi/pdf/10.1073/pnas.2112887119

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