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

MAbs
Yme U van der VeldenMarit J VAN Gils

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.

References

Oct 30, 2012·Nature·Florian KleinMichel C Nussenzweig
Mar 5, 2014·Nature·Nicole A Doria-RoseJohn R Mascola
Aug 30, 2014·Trends in Microbiology·Marit J van Gils, Rogier W Sanders
Nov 26, 2014·Proceedings of the National Academy of Sciences of the United States of America·Devin SokDennis R Burton
Mar 3, 2015·Current Opinion in HIV and AIDS·Ann J Hessell, Nancy L Haigwood
Dec 25, 2015·Science Translational Medicine·Rebecca M LynchUNKNOWN VRC 601 Study Team
Dec 14, 2016·The New England Journal of Medicine·Katharine J BarTae-Wook Chun
Jan 17, 2017·Nature Medicine·Marina CaskeyFlorian Klein
Sep 22, 2017·Science Translational Medicine·Boris JulgDan H Barouch
Jul 14, 2018·AIDS Research and Human Retroviruses·Yme U van der VeldenMarit J van Gils
Sep 28, 2018·Nature·Pilar MendozaMichel C Nussenzweig
Oct 18, 2018·Retrovirology·Laura E McCoy
Aug 16, 2019·Cell Host & Microbe·Christine A BricaultBette Korber

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Methods Mentioned

BETA
glycosylation
transfection
transfect
flow cytometry

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