Diverse HIV-1 escape pathways from broadly neutralizing antibody PGDM1400 in humanized mice

Yme U van der Velden; Julien Villaudy; Esther Siteur-van Rijnstra; Cynthia A van der Linden; Monique A Vink; Edith E Schermer; Kees Weijer; Ben Berkhout; Rogier W Sanders; Marit J van Gils

doi:10.1080/19420862.2020.1845908

Diverse HIV-1 escape pathways from broadly neutralizing antibody PGDM1400 in humanized mice

MAbs. 2020 Jan-Dec;12(1):1845908. doi: 10.1080/19420862.2020.1845908.

Authors

Affiliations

¹ Department of Medical Microbiology, Amsterdam UMC, AMC, University of Amsterdam , Amsterdam, the Netherlands.
² AIMM Therapeutics , Amsterdam, the Netherlands.
³ HIS mouse facility, Amsterdam UMC, AMC, University of Amsterdam , Amsterdam, the Netherlands.
⁴ Department of Microbiology and Immunology, Weill Medical College of Cornell University , New York, NY, USA.

Abstract

Recent studies have shown the potential of broadly neutralizing antibodies (bnAbs) for HIV-1 treatment. One of the candidate antibodies moving into clinical trials is the bnAb PGDM1400. Here, we studied the therapeutic potency and escape pathways of bnAb PGDM1400 during monovalent therapy in human immune system (HIS) mice using the BG505, REJO, MJ4 and AMC008 virus isolates. PGDM1400 administered during chronic infection caused a modest decrease in viral load in the first week of administration in 7 out of 10 animals, which correlated with the in vitro neutralization sensitivity of the viruses to PGDM1400. As expected for monotherapy, viral loads rebounded after about a week and different viral escape pathways were observed, involving the deletion of glycans in the envelope glycoprotein at positions 130 or 160. (Pre)clinical trials should reveal whether PGDM1400 is a useful component of an antibody combination treatment or as part of a tri-specific antibody.

Keywords: HIV-1; PGDM1400; broadly neutralizing antibody; human immune system mouse; therapeutic; viral escape.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Broadly Neutralizing Antibodies / immunology*
HIV Antibodies / immunology*
HIV Infections / immunology*
HIV-1 / immunology*
Humans
Mice

Substances

Broadly Neutralizing Antibodies
HIV Antibodies

Grants and funding

This work was supported by the Eurostars [E!10239]; Nederlandse Organisatie voor Wetenschappelijk Onderzoek [veni#016171112]; Nederlandse Organisatie voor Wetenschappelijk Onderzoek [vici#91818627]; ZonMw [40-42600-98-705]; amfAR, The Foundation for AIDS Research [109514-61-RKVA].