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© Research
Publication : mBio

Neutralization properties of simian immunodeficiency viruses infecting chimpanzees and gorillas

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in mBio - 21 Apr 2015

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

Link to Pubmed [PMID] – 25900654

MBio 2015;6(2)

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.

http://www.ncbi.nlm.nih.gov/pubmed/25900654