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Neutralizing human monoclonal antibodies prevent Zika virus infection in macaques

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Science Translational Medicine  04 Oct 2017:
Vol. 9, Issue 410, eaan8184
DOI: 10.1126/scitranslmed.aan8184
  • Fig. 1. The plasmablast-derived human nmAbs SMZAb1, SMZAb2, and SMZAb5 neutralize ZIKV in vitro.

    Ninety-one mAbs generated from a ZIKV-infected patient were screened for ZIKV neutralization potency using Vero cell infectivity assays, and the three most potent—SMZAb1, SMZAb2, and SMZAb5—neutralized ZIKV at low concentrations. The neutralization titers were determined by focus reduction neutralization test (FRNT).

  • Fig. 2. Study design and pharmacokinetics of SMZAb cocktail administration to Indian rhesus macaques.

    (A) A cocktail containing the three nmAbs—SMZAb1, SMZAb2, and SMZAb5—at a dose of 20 mg kg−1 each were administered to four rhesus macaques (group 1). A control group (group 2) received the human CB1 isotype control at a dose of 60 mg kg−1 total. All animals were challenged with 1000 PFU of ZIKV Rio U-1 2016 1 day after mAb administration. Serum was collected at the indicated time points for viral load, neutralization, IgG, and IgM measurements. (B) Serum levels of recombinant antibodies were determined by ELISA. Antibody level values for each SMZAb cocktail (blue) or control mAb (open symbols) animal. (C) Median values for group 1 (blue) and group 2 (open symbols). (D) ZIKV-neutralizing activity in serum after mAb infusion was determined by FRNT. Median ZIKV foci neutralization percentage values for each SMZAb cocktail (blue) or control mAb (open symbols) animal. (E) Median values for group 1 (blue) and group 2 (open symbols).

  • Fig. 3. Viral loads and humoral responses after ZIKV challenge.

    (A) A cocktail containing the three nmAbs—SMZAb1, SMZAb2, and SMZAb5—at a dose of 20 mg kg−1 each were administered to four rhesus macaques (group 1). A control group (group 2) received the human CB1 isotype control at a dose of 60 mg kg−1 total. All animals were challenged with 1000 PFU of ZIKV Rio U-1 2016 1 day after mAb administration. Serum viral loads for SMZAb-treated macaques (blue) and control CB1 mAb–treated macaques (open symbols). Dotted lines indicate the limit of detection (LOD) of the assay. humAb, human antibody. (B) Humoral IgM and IgG responses of challenged animals against whole ZIKV or NS1. Serum binding (diluted 1:100) was measured by ELISA using rhesus-specific antibodies.

Supplementary Materials

  • www.sciencetranslationalmedicine.org/cgi/content/full/9/410/eaan8184/DC1

    Fig. S1. Plasmablast-derived human mAbs neutralize ZIKV in vitro.

    Fig. S2. Epitope mapping: SMZAb1, SMZAb2, and SMZAb5 ZIKV E protein epitope specificity was evaluated.

    Fig. S3. Binding of SMZAb1, SMZAb2, and SMZAb5 to whole ZIKV or DENV was evaluated by virus capture ELISA using 4G2.

    Fig. S4. DENV neutralization by SMZAbs.

    Fig. S5. ZIKV-neutralizing activity after mAb infusion (FRNT).

    Table S1. SMZAb amino acid sequences.

    Table S2. Neutralization of ZIKV strains and DENV serotypes by SMZAbs (FRNT50 μg ml−1).

    Table S3. ZIKV Paraiba/2015 neutralization by SMZAbs before infusion.

    Table S4. Study animals.

    Table S5. Viral titers (log10 PFU ml−1) in serum after ZIKV challenge.

    Table S6. Viral titers (vRNA copies ml−1) in serum after ZIKV challenge.

  • Supplementary Material for:

    Neutralizing human monoclonal antibodies prevent Zika virus infection in macaques

    Diogo M. Magnani, Thomas F. Rogers, Nathan Beutler, Michael J. Ricciardi, Varian K. Bailey, Lucas Gonzalez-Nieto, Bryan Briney, Devin Sok, Khoa Le, Alexander Strubel, Martin J. Gutman, Núria Pedreño-Lopez, Nathan D. Grubaugh, Cassia G. T. Silveira, Helen S. Maxwell, Aline Domingues, Mauricio A. Martins, David E. Lee, Erica E. Okwuazi, Sherrie Jean, Elizabeth A. Strobert, Ann Chahroudi, Guido Silvestri, Thomas H. Vanderford, Esper G. Kallas, Ronald C. Desrosiers, Myrna C. Bonaldo, Stephen S. Whitehead, Dennis R. Burton,* David I. Watkins*

    *Corresponding author. Email: burton{at}scripps.edu (D.R.B.); dwatkins{at}med.miami.edu (D.I.W.)

    Published 4 October 2017, Sci. Transl. Med. 9, eaan8184 (2017)
    DOI: 10.1126/scitranslmed.aan8184

    This PDF file includes:

    • Fig. S1. Plasmablast-derived human mAbs neutralize ZIKV in vitro.
    • Fig. S2. Epitope mapping: SMZAb1, SMZAb2, and SMZAb5 ZIKV E protein epitope specificity was evaluated.
    • Fig. S3. Binding of SMZAb1, SMZAb2, and SMZAb5 to whole ZIKV or DENV was evaluated by virus capture ELISA using 4G2.
    • Fig. S4. DENV neutralization by SMZAbs.
    • Fig. S5. ZIKV-neutralizing activity after mAb infusion (FRNT).
    • Table S1. SMZAb amino acid sequences.
    • Table S2. Neutralization of ZIKV strains and DENV serotypes by SMZAbs (FRNT50 μg ml−1).
    • Table S3. ZIKV Paraiba/2015 neutralization by SMZAbs before infusion.
    • Table S4. Study animals.
    • Table S5. Viral titers (log10 PFU ml−1) in serum after ZIKV challenge.
    • Table S6. Viral titers (vRNA copies ml−1) in serum after ZIKV challenge.

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