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Neutralization properties of simian immunodeficiency viruses infecting chimpanzees and gorillas.

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Date
2015-04-21
Authors
Barbian, Hannah J
Decker, Julie M
Bibollet-Ruche, Frederic
Galimidi, Rachel P
West, Anthony P
Learn, Gerald H
Parrish, Nicholas F
Iyer, Shilpa S
Li, Yingying
Pace, Craig S
Song, Ruijiang
Huang, Yaoxing
Denny, Thomas N
Mouquet, Hugo
Martin, Loic
Acharya, Priyamvada
Zhang, Baoshan
Kwong, Peter D
Mascola, John R
Verrips, C Theo
Strokappe, Nika M
Rutten, Lucy
McCoy, Laura E
Weiss, Robin A
Brown, Corrine S
Jackson, Raven
Silvestri, Guido
Connors, Mark
Burton, Dennis R
Shaw, George M
Nussenzweig, Michel C
Bjorkman, Pamela J
Ho, David D
Farzan, Michael
Hahn, Beatrice H
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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 article
Subject
Animals
Antibodies, Neutralizing
Cross Reactions
Gorilla gorilla
HIV Antibodies
Humans
Inhibitory Concentration 50
Neutralization Tests
Pan troglodytes
Simian Acquired Immunodeficiency Syndrome
Simian Immunodeficiency Virus
Permalink
https://hdl.handle.net/10161/13347
Published Version (Please cite this version)
10.1128/mBio.00296-15
Publication 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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Scholars@Duke

Acharya

Priyamvada Acharya

Associate Professor in Surgery
Denny

Thomas Norton Denny

Professor in Medicine
Thomas N. Denny, MSc, M.Phil, is the Chief Operating Officer of the Duke Human Vaccine Institute (DHVI) and the Center for HIV/AIDS Vaccine Immunology (CHAVI), 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. He has recently been appointed to the Duke University Fuqua School of Business Health Sector Advisory Council. Previously, he was an Associate Professor of Pathology, Laboratory M
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