Research ArticleHIV

Broadly neutralizing antibodies targeting the HIV-1 envelope V2 apex confer protection against a clade C SHIV challenge

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Science Translational Medicine  06 Sep 2017:
Vol. 9, Issue 406, eaal1321
DOI: 10.1126/scitranslmed.aal1321
  • Fig. 1. Plasma viral loads and CD4+ T cell counts in rhesus macaques challenged with SHIV-325c.

    (A) Plasma viral RNA (log RNA copies/ml) are shown for animals that were challenged intrarectally with SHIV-325c. The red line represents the mean log RNA copies/ml. (B) CD4+ T cell numbers in the same animals before and after SHIV-325c infection (P = 0.016, paired t test).

  • Fig. 2. Neutralization profiles of PGDM1400 and CAP256-VRC26.25 against multiclade pseudoviruses.

    (A) Each bar represents the IC80 (μg/ml) of PGDM1400 (top graph) or CAP256-VRC26.25 (bottom graph) against a single virus. Viruses are ranked according to increasing IC80 values. Bars reaching the dotted line represent IC80 values >50 μg/ml. The red bars highlight the IC80 values against SHIV-325c. (B) IC80 values for PGDM1400 and CAP256-VRC26.25 against SHIV-325c (red dot) and against the clade C pseudoviruses included in (A). The horizontal bars represent the mean of IC80 values of neutralizable pseudoviruses.

  • Fig. 3. Neutralization of SHIV-325c by CAP256-VRC26.25, PGDM1400, and PG9.

    Neutralization was measured using replication-competent challenge stock SHIV-325c infection of TZM-bl cells.

  • Fig. 4. Protective efficacy of PGDM1400 and CAP256-VRC26.25-LS against SHIV-325c in rhesus macaques.

    Plasma viral RNA (vRNA) (log RNA copies/ml) are shown for animals that received saline control (A), PGDM1400 (2 mg/kg) (B), CAP256-VRC26.25-LS (2 mg/kg) (C), PGDM1400 (0.4 mg/kg) (D), CAP256-VRC26.25-LS (0.4 mg/kg) (E), PGDM1400 (0.08 mg/kg) (F), or CAP256-VRC26.25-LS (0.08 mg/kg) (G). The assay sensitivity limit was >50 RNA copies/ml.

  • Fig. 5. Serum concentrations of CAP256-VRC26.25-LS and PGDM1400 in antibody-treated animals.

    Serum antibody concentrations of CAP256-VRC26.25-LS (A) and PGDM1400 (B) were determined by ELISA. The dotted vertical line marks the day of SHIV challenge.

  • Fig. 6. Analysis of SHIV-325c V1V2 envelope sequences in breakthrough infections.

    Single-genome envelope amplification was performed with plasma viral RNA on day 28. For one saline control animal, H515, viral amplification failed and therefore is not shown here. The env sequence at the top presents the SHIV-325c molecular clone inoculum. The column on the right reports the frequency of distinct amplicons (based on unique sequence variations in V1V2) per total env amplicons obtained from a given animal.

  • Fig. 7. Potency and breadth profiles of single and combination bNAbs against 200 clade C HIV-1 Env pseudoviruses.

    (A) Heat maps of IC80 values for single bNAbs and bNAb combinations. Rows represent Env pseudoviruses, and columns represent single and combination bNAbs. Darker hues of red indicate more potent neutralization, and gray cells indicate IC80 above threshold. (B) Potency-breadth curves for single bNAbs and bNAb combinations are shown. IC80 scores for combinations and single bNAbs were compared using Wilcoxon rank-sum test. Antibody a, PGDM1400; antibody b, CAP256-VRC26.25; antibody c, PGT121.

  • Table 1. Neutralization profiles of PGDM1400, CAP256-VRC26.25, and PG9 against SHIV challenge stocks.

    IC50 and IC80 values are in micrograms per milliliter. Values between 0.001 and 0.01 μg/ml are highlighted in red; between 0.01 and 0.1 μg/ml, orange; between 0.1 and 1 μg/ml, yellow; between 1 and 10 μg/ml, light green; and between 10 and 50 μg/ml, dark green. Virus suffix indicates PBMC cell type used for production: .Rh, rhesus PBMCs; .Hu, human PBMCs.


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  • Table 2. Neutralization properties of three different SHIV viruses in TZM-bl assays against a panel of bNAbs targeting distinct epitopes.

    IC50 and IC80 values are in micrograms per milliliter. Values between 0.001 and 0.01 μg/ml are highlighted in red; between 0.01 and 0.1 μg/ml, orange; between 0.1 and 1 μg/ml, yellow; between 1 and 10 μg/ml, light green; and between 10 and 50 μg/ml, dark green.


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Supplementary Materials

  • www.sciencetranslationalmedicine.org/cgi/content/full/9/406/eaal1321/DC1

    Fig. S1. Highlighter amino acid sequence alignment of env derived from the SHIV-325c stock and the parental HIV-1 env.

    Fig. S2. Serum concentration of CAP256-VRC26.25-LS and CAP256-VRC26.25 in naïve, uninfected rhesus macaques.

    Table S1. IC80 (μg/ml) values of PGDM1400 and CAP256-VRC26.25 against SHIV-325c and a multiclade panel of 208 HIV-1 pseudoviruses.

    Table S2. Neutralization of JR-CSF alanine variants by PGDM1400 or PG9.

    Table S3. Primary data for Fig. 1 and fig. S2.

  • Supplementary Material for:

    Broadly neutralizing antibodies targeting the HIV-1 envelope V2 apex confer protection against a clade C SHIV challenge

    Boris Julg, Lawrence J. Tartaglia, Brandon F. Keele, Kshitij Wagh, Amarendra Pegu, Devin Sok, Peter Abbink, Stephen D. Schmidt, Keyun Wang, Xuejun Chen, M. Gordon Joyce, Ivelin S. Georgiev, Misook Choe, Peter D. Kwong, Nicole A. Doria-Rose, Khoa Le, Mark K. Louder, Robert T. Bailer, Penny L. Moore, Bette Korber, Michael S. Seaman, Salim S. Abdool Karim, Lynn Morris, Richard A. Koup, John R. Mascola, Dennis R. Burton, Dan H. Barouch*

    *Corresponding author. Email: dbarouch{at}bidmc.harvard.edu

    Published 6 September 2017, Sci. Transl. Med. 9, eaal1321 (2017)
    DOI: 10.1126/scitranslmed.aal1321

    This PDF file includes:

    • Fig. S1. Highlighter amino acid sequence alignment of env derived from the SHIV-325c stock and the parental HIV-1 env.
    • Fig. S2. Serum concentration of CAP256-VRC26.25-LS and CAP256-VRC26.25 in naïve, uninfected rhesus macaques.
    • Table S1. IC80 (μg/ml) values of PGDM1400 and CAP256-VRC26.25 against SHIV-325c and a multiclade panel of 208 HIV-1 pseudoviruses.
    • Table S2. Neutralization of JR-CSF alanine variants by PGDM1400 or PG9.
    • Table S3. Primary data for Fig. 1 and fig. S2.

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