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Neutralization Properties of Simian Immunodeficiency Viruses Infecting Chimpanzees and Gorillas

Hannah Barbian 1 Julie Decker 2 Frederic Bibollet-Ruche 1 Rachel Galimidi 3 Anthony West 3 Gerald H Learn 1 Nicholas F Parrish 1 Shilpa Iyer 1 Yingying Li 1 Craig Pace 4 Ruijiang Song 5 Yaoxing Huang 5 Thomas Denny 6 Hugo Mouquet 7, 8 Loïc M Martin 9 Priyamvada Acharya 10 Baoshan Zhang 10 Peter D. Kwong 10 John R. Mascola 10 C. Theo Verrips 11 Nika Strokappe 12 Lucy Rutten 12 Laura Mccoy 13 Robin Weiss 13 Corrine Brown 14 Raven Jackson 14 Guido Silvestri 15 Mark Connors 16 Dennis Burton 17 George Shaw 1 Michel C. Nussenzweig 18 Pamela Bjorkman 3 David Ho 5 Michael Farzan 17 Beatrice H Hahn 1 
Abstract : 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-Igmim2, 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.
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Hannah Barbian, Julie Decker, Frederic Bibollet-Ruche, Rachel Galimidi, Anthony West, et al.. Neutralization Properties of Simian Immunodeficiency Viruses Infecting Chimpanzees and Gorillas. mBio, American Society for Microbiology, 2015, 6 (2), ⟨10.1128/mBio.00296-15⟩. ⟨cea-02530869⟩



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