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Neutralization properties of simian immunodeficiency viruses infecting chimpanzees and gorillas.

Publication ,  Journal Article
Barbian, HJ; Decker, JM; Bibollet-Ruche, F; Galimidi, RP; West, AP; Learn, GH; Parrish, NF; Iyer, SS; Li, Y; Pace, CS; Song, R; Huang, Y ...
Published in: mBio
April 21, 2015

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.

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Published In

mBio

DOI

EISSN

2150-7511

Publication Date

April 21, 2015

Volume

6

Issue

2

Location

United States

Related Subject Headings

  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • Pan troglodytes
  • Neutralization Tests
  • Inhibitory Concentration 50
  • Humans
  • HIV Antibodies
  • Gorilla gorilla
  • Cross Reactions
 

Citation

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Chicago
ICMJE
MLA
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Barbian, H. J., Decker, J. M., Bibollet-Ruche, F., Galimidi, R. P., West, A. P., Learn, G. H., … Hahn, B. H. (2015). Neutralization properties of simian immunodeficiency viruses infecting chimpanzees and gorillas. MBio, 6(2). https://doi.org/10.1128/mBio.00296-15
Barbian, Hannah J., Julie M. Decker, Frederic Bibollet-Ruche, Rachel P. Galimidi, Anthony P. West, Gerald H. Learn, Nicholas F. Parrish, et al. “Neutralization properties of simian immunodeficiency viruses infecting chimpanzees and gorillas.MBio 6, no. 2 (April 21, 2015). https://doi.org/10.1128/mBio.00296-15.
Barbian HJ, Decker JM, Bibollet-Ruche F, Galimidi RP, West AP, Learn GH, et al. Neutralization properties of simian immunodeficiency viruses infecting chimpanzees and gorillas. mBio. 2015 Apr 21;6(2).
Barbian, Hannah J., et al. “Neutralization properties of simian immunodeficiency viruses infecting chimpanzees and gorillas.MBio, vol. 6, no. 2, Apr. 2015. Pubmed, doi:10.1128/mBio.00296-15.
Barbian HJ, Decker JM, Bibollet-Ruche F, Galimidi RP, West AP, Learn GH, Parrish NF, Iyer SS, Li Y, Pace CS, Song R, Huang Y, Denny TN, Mouquet H, Martin L, Acharya P, Zhang B, Kwong PD, Mascola JR, Verrips CT, Strokappe NM, Rutten L, McCoy LE, Weiss RA, Brown CS, Jackson R, Silvestri G, Connors M, Burton DR, Shaw GM, Nussenzweig MC, Bjorkman PJ, Ho DD, Farzan M, Hahn BH. Neutralization properties of simian immunodeficiency viruses infecting chimpanzees and gorillas. mBio. 2015 Apr 21;6(2).

Published In

mBio

DOI

EISSN

2150-7511

Publication Date

April 21, 2015

Volume

6

Issue

2

Location

United States

Related Subject Headings

  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • Pan troglodytes
  • Neutralization Tests
  • Inhibitory Concentration 50
  • Humans
  • HIV Antibodies
  • Gorilla gorilla
  • Cross Reactions