Diverse HIV-1 escape pathways from broadly neutralizing antibody PGDM1400 in humanized mice. Issue 1 (1st January 2020)

• Record Type: Journal Article
• Authors: van der Velden, Yme U.; Villaudy, Julien; Siteur - van Rijnstra, Esther; van der Linden, Cynthia A.; Vink, Monique A.; Schermer, Edith E.; Weijer, Kees; Berkhout, Ben; Sanders, Rogier W.; van Gils, Marit J.
• Is Part Of: MAbs. Volume 12:Issue 1(2020)
• Publication Date: 2020-01-01
• Subjects: HIV-1 -- broadly neutralizing antibody -- PGDM1400 -- therapeutic -- human immune system mouse -- viral escape; Monoclonal antibodies -- Therapeutic use -- Periodicals; Monoclonal antibodies -- Periodicals; Antibodies, Monoclonal -- Periodicals; 616.0798
• DOI: 10.1080/19420862.2020.1845908
• Languages: English
• ISSNs: 1942-0862

Abstract

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.