Neutralization properties of simian immunodeficiency viruses infecting chimpanzees and gorillas.
Abstract
UNLABELLED: Broadly cross-reactive neutralizing antibodies (bNabs) represent powerful
tools to combat human immunodeficiency virus type 1 (HIV-1) infection. Here, we examined
whether HIV-1-specific bNabs are capable of cross-neutralizing distantly related simian
immunodeficiency viruses (SIVs) infecting central (Pan troglodytes troglodytes) (SIVcpzPtt)
and eastern (Pan troglodytes schweinfurthii) (SIVcpzPts) chimpanzees (n = 11) as well
as western gorillas (Gorilla gorilla gorilla) (SIVgor) (n = 1). We found that bNabs
directed against the CD4 binding site (n = 10), peptidoglycans at the base of variable
loop 3 (V3) (n = 5), and epitopes at the interface of surface (gp120) and membrane-bound
(gp41) envelope glycoproteins (n = 5) failed to neutralize SIVcpz and SIVgor strains.
In addition, apex V2-directed bNabs (n = 3) as well as llama-derived (heavy chain
only) antibodies (n = 6) recognizing both the CD4 binding site and gp41 epitopes were
either completely inactive or neutralized only a fraction of SIVcpzPtt strains. In
contrast, one antibody targeting the membrane-proximal external region (MPER) of gp41
(10E8), functional CD4 and CCR5 receptor mimetics (eCD4-Ig, eCD4-Ig(mim2), CD4-218.3-E51,
and CD4-218.3-E51-mim2), as well as mono- and bispecific anti-human CD4 (iMab and
LM52) and CCR5 (PRO140, PRO140-10E8) receptor antibodies neutralized >90% of SIVcpz
and SIVgor strains with low-nanomolar (0.13 to 8.4 nM) potency. Importantly, the latter
antibodies blocked virus entry not only in TZM-bl cells but also in Cf2Th cells expressing
chimpanzee CD4 and CCR5 and neutralized SIVcpz in chimpanzee CD4(+) T cells, with
50% inhibitory concentrations (IC50s) ranging from 3.6 to 40.5 nM. These findings
provide new insight into the protective capacity of anti-HIV-1 bNabs and identify
candidates for further development to combat SIVcpz infection. IMPORTANCE: SIVcpz
is widespread in wild-living chimpanzees and can cause AIDS-like immunopathology and
clinical disease. HIV-1 infection of humans can be controlled by antiretroviral therapy;
however, treatment of wild-living African apes with current drug regimens is not feasible.
Nonetheless, it may be possible to curb the spread of SIVcpz in select ape communities
using vectored immunoprophylaxis and/or therapy. Here, we show that antibodies and
antibody-like inhibitors developed to combat HIV-1 infection in humans are capable
of neutralizing genetically diverse SIVcpz and SIVgor strains with considerable breadth
and potency, including in primary chimpanzee CD4(+) T cells. These reagents provide
an important first step toward translating intervention strategies currently developed
to treat and prevent AIDS in humans to SIV-infected apes.
Type
Journal articleSubject
AnimalsAntibodies, Neutralizing
Cross Reactions
Gorilla gorilla
HIV Antibodies
Humans
Inhibitory Concentration 50
Neutralization Tests
Pan troglodytes
Simian Acquired Immunodeficiency Syndrome
Simian Immunodeficiency Virus
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https://hdl.handle.net/10161/13347Published Version (Please cite this version)
10.1128/mBio.00296-15Publication Info
Barbian, Hannah J; Decker, Julie M; Bibollet-Ruche, Frederic; Galimidi, Rachel P;
West, Anthony P; Learn, Gerald H; ... Hahn, Beatrice H (2015). Neutralization properties of simian immunodeficiency viruses infecting chimpanzees
and gorillas. MBio, 6(2). 10.1128/mBio.00296-15. Retrieved from https://hdl.handle.net/10161/13347.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Priyamvada Acharya
Associate Professor in Surgery
Thomas Norton Denny
Professor in Medicine
Thomas N. Denny, MSc, M.Phil, is the Chief Operating Officer of the Duke Human Vaccine
Institute (DHVI), Associate Dean for Duke Research and Discovery @RTP, and a Professor
of Medicine in the Department of Medicine at Duke University Medical Center. He is
also an Affiliate Member of the Duke Global Health Institute. Previously, he served
on the Health Sector Advisory Council of the Duke University Fuquay School of Business.
Prior to joining Duke, he was an Associate Professor of Pathology, Labo
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