UMMS Affiliation

MassBiologics

Publication Date

2021-06-07

Document Type

Article

Disciplines

Immunology of Infectious Disease | Immunoprophylaxis and Therapy | Virus Diseases

Abstract

In the absence of a prophylactic vaccine, the use of antiretroviral therapy (ART) as pre-exposure prophylaxis (PrEP) to prevent HIV acquisition by uninfected individuals is a promising approach to slowing the epidemic, but its efficacy is hampered by incomplete patient adherence and ART-resistant variants. Here, we report that competitive inhibition of HIV Env-CCR5 binding via the CCR5-specific antibody Leronlimab protects rhesus macaques against infection following repeated intrarectal challenges of CCR5-tropic SHIVSF162P3. Injection of Leronlimab weekly at 10 mg/kg provides significant but partial protection, while biweekly 50 mg/kg provides complete protection from SHIV acquisition. Tissue biopsies from protected macaques post challenge show complete CCR5 receptor occupancy and an absence of viral nucleic acids. After Leronlimab washout, protected macaques remain aviremic, and adoptive transfer of hematologic cells into naive macaques does not transmit viral infection. These data identify CCR5 blockade with Leronlimab as a promising approach to HIV prophylaxis and support initiation of clinical trials.

Keywords

Antibody therapy, HIV infections

Rights and Permissions

Copyright © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

DOI of Published Version

10.1038/s41467-021-23697-6

Source

Chang XL, Webb GM, Wu HL, Greene JM, Abdulhaqq S, Bateman KB, Reed JS, Pessoa C, Weber WC, Maier N, Chew GM, Gilbride RM, Gao L, Agnor R, Giobbi T, Torgerson J, Siess D, Burnett N, Fischer M, Shiel O, Moats C, Patterson B, Dhody K, Kelly S, Pourhassan N, Magnani DM, Smedley J, Bimber BN, Haigwood NL, Hansen SG, Brown TR, Ndhlovu LC, Sacha JB. Antibody-based CCR5 blockade protects Macaques from mucosal SHIV transmission. Nat Commun. 2021 Jun 7;12(1):3343. doi: 10.1038/s41467-021-23697-6. PMID: 34099693; PMCID: PMC8184841. Link to article on publisher's site

Journal/Book/Conference Title

Nature communications

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

34099693

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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