Fc-dependent functions are redundant to efficacy of anti-HIV antibody PGT121 in macaques.

J Clin Invest 2019 01 26;129(1):182-191. Epub 2018 Nov 26.

Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, and.

A considerable body of evidence suggests that Fc-dependent functions improve the capacity of broadly neutralizing antibodies (BnAbs) to protect against and control HIV-1 infection. This phenomenon, however, has not been formally tested in robust cell-associated macaque simian-human immunodeficiency virus (SHIV) models with newer-generation BnAbs. We studied both the WT BnAb PGT121 and a LALA mutant of PGT121 (which has impaired Fc-dependent functions) for their ability to protect pigtail macaques from an i.v. high-dose cell-associated SHIVSF162P3 challenge. We found that both WT and LALA PGT121 completely protected all 12 macaques studied. Further, partial depletion of NK cells, key mediators of Fc-dependent functions, did not abrogate the protective efficacy of PGT121 in 6 macaques. Additionally, in animals with established SHIVSF162P3 infection, SHIV viremia levels were equally rapidly reduced by LALA and WT PGT121. Our studies suggest that the potent neutralizing capacity of PGT121 renders the Fc-dependent functions of the Ab at least partially redundant. These findings have implications for Ab-mediated protection from and control of HIV-1 infection.

Download full-text PDF

Source
http://dx.doi.org/10.1172/JCI122466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307963PMC
January 2019
4 Reads

Publication Analysis

Top Keywords

fc-dependent functions
20
hiv-1 infection
8
pgt121 macaques
8
lala pgt121
8
control hiv-1
8
pgt121
7
fc-dependent
5
pgt121 completely
4
completely protected
4
key mediators
4
challenge lala
4
shivsf162p3 challenge
4
cells key
4
depletion cells
4
studied partial
4
cell-associated shivsf162p3
4
partial depletion
4
protected macaques
4
macaques studied
4
pigtail macaques
4

References

(Supplied by CrossRef)
Basis and statistical design of the passive HIV-1 antibody mediated prevention (AMP) test-of-concept efficacy trials
Gilbert et al.
Stat Commun Infect Dis 2017
Genetic characterization of human immunodeficiency virus type 1 in blood and genital secretions: evidence for viral compartmentalization and selection during sexual transmission
Zhu et al.
J Virol 1996

Similar Publications