TY - JOUR
T1 - Effector function does not contribute to protection from virus challenge by a highly potent HIV broadly neutralizing antibody in nonhuman primates
AU - Hangartner, Lars
AU - Beauparlant, David
AU - Rakasz, Eva
AU - Nedellec, Rebecca
AU - Hozé, Nathanaël
AU - McKenney, Katherine
AU - Martins, Mauricio A.
AU - Seabright, Gemma E.
AU - Allen, Joel D.
AU - Weiler, Andrea M.
AU - Friedrich, Thomas C.
AU - Regoes, Roland R.
AU - Crispin, Max
AU - Burton, Dennis R.
N1 - Funding Information:
This work was funded by NIH grants 5R37 A1055332 and UM1AI100663 to D.R.B. and UM1AI144462 to D.R.B. and L.H. The Swiss National Science Foundation Fellowship P2ZHP3_174834 supported D.B. This NHP study was performed at the WNPRC supported, in part, by the NCRR grant P51OD011106. M.A.M. was supported by K01 0D023032 from the Office of the Director, NIH.
Publisher Copyright:
Copyright © 2021 The Authors, some rights reserved.
PY - 2021/3/17
Y1 - 2021/3/17
N2 - Protection from immunodeficiency virus challenge in nonhuman primates (NHPs) by a first-generation HIV broadly neutralizing antibody (bnAb) b12 has previously been shown to benefit from interaction between the bnAb and Fcγ receptors (FcγRs) on immune cells. To investigate the mechanism of protection for a more potent second-generation bnAb currently in clinical trials, PGT121, we carried out a series of NHP studies. These studies included treating with PGT121 at a concentration at which only half of the animals were protected to avoid potential masking of FcγR effector function benefits by dominant neutralization and using a new variant that more completely eliminated all rhesus FcγR binding than earlier variants. In contrast to b12, which required FcγR binding for optimal protection, we concluded that PGT121-mediated protection is not augmented by FcγR interaction. Thus, for HIV-passive antibody prophylaxis, these results, together with existing literature, emphasize the importance of neutralization potency for clinical antibodies, with effector function requiring evaluation for individual antibodies.
AB - Protection from immunodeficiency virus challenge in nonhuman primates (NHPs) by a first-generation HIV broadly neutralizing antibody (bnAb) b12 has previously been shown to benefit from interaction between the bnAb and Fcγ receptors (FcγRs) on immune cells. To investigate the mechanism of protection for a more potent second-generation bnAb currently in clinical trials, PGT121, we carried out a series of NHP studies. These studies included treating with PGT121 at a concentration at which only half of the animals were protected to avoid potential masking of FcγR effector function benefits by dominant neutralization and using a new variant that more completely eliminated all rhesus FcγR binding than earlier variants. In contrast to b12, which required FcγR binding for optimal protection, we concluded that PGT121-mediated protection is not augmented by FcγR interaction. Thus, for HIV-passive antibody prophylaxis, these results, together with existing literature, emphasize the importance of neutralization potency for clinical antibodies, with effector function requiring evaluation for individual antibodies.
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U2 - 10.1126/scitranslmed.abe3349
DO - 10.1126/scitranslmed.abe3349
M3 - Article
C2 - 33731434
AN - SCOPUS:85103039192
VL - 13
JO - Science Translational Medicine
JF - Science Translational Medicine
SN - 1946-6234
IS - 585
M1 - eabe3349
ER -