Research ArticleHIV

Antigenic competition in CD4+ T cell responses in a randomized, multicenter, double-blind clinical HIV vaccine trial

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Science Translational Medicine  20 Nov 2019:
Vol. 11, Issue 519, eaaw1673
DOI: 10.1126/scitranslmed.aaw1673
  • Fig. 2 Gag/Pol-specific T cell responses in HVTN 084 1 month after vaccination in participants receiving rAd5 expressing Gag/Pol/Env (with Env) or Gag/Pol (without Env).

    Background-adjusted magnitude of (A) CD4+ and (B) CD8+ T cells producing IFN-γ and/or IL-2 measured by ICS. Box plots represent the distribution for the positive responders only, where the midline of the box denotes the median and the ends of the box denote the 25th and 75th percentiles, with whiskers extended to the extreme data points that are no more than 1.5 times the interquartile range or, if no value meets this criterion, to the data extremes. The box plots are overlaid with individual data points of both positive (in red circles) and negative responders (in blue triangles). Percentages above the boxes are response rates.

  • Fig. 3 Expression of different combinations of functional markers by CD4+ and CD8+ T cells.

    Heat map of COMPASS posterior probabilities for Gag-specific CD4+ (A) and CD8+ T cells (C) and Pol-specific CD4+ (B) and CD8+ T cells (D). Columns correspond to the different cell subsets modeled by COMPASS, color-coded by the cytokines they express (white, “off”; shaded, “on”; grouped by color, “degree of functionality”), and ordered by degree of functionality from one function on the left to six functions on the right. Subsets with maximum posterior probabilities less than 0.005 are removed from the heat map. Rows correspond to participants in treatment (Trt) group 1 (red) and group 2 (blue). Each cell shows the probability that the corresponding cell subset (column) exhibits an antigen-specific response in the corresponding participant (row), where the probability is color-coded from white (zero) to purple (one). The participant-level posterior probabilities reflect the certainty from the COMPASS model that the subset exhibits an antigen-specific response in a participant [i.e., that the magnitude of the stimulated sample is above the magnitude of the (paired) nonstimulated sample].

  • Fig. 4 Functionality scores for Gag- and Pol-specific T cell responses in HVTN 084 1 month after vaccination in participants receiving rAd5 expressing Gag/Pol/Env (red) or Gag/Pol (blue).

    Functionality scores from COMPASS are defined as the proportion of antigen-specific subsets detected among all possible ones based on expression of IFN-γ, IL-2, TNF-α, CD40L, IL-4, and GzB by CD4+ T cells (A and B) and CD8+ T cells (C and D) for Gag and Pol, respectively. P values are based on Wilcoxon rank sum test.

  • Fig. 5 Distribution of epitopes for Gag- and Pol-specific T cell responses in HVTN 084.

    Epitope mapping was performed 1 month after vaccination by IFN-γ ELISpot by deconvoluting responses to pools down to single 15-mer peptides. Responses to peptides overlapping by eight or more amino acids are shown as one epitope for (A) Gag and (B) Pol. Group 1 (immunized with Env) is shown in red; group 2 (immunized without Env) is shown in blue. Each row represents a single individual; empty rows represent subjects for which no individual epitopes were identified.

  • Fig. 6 Epitope breadth of Gag/Pol-specific T cell responses in HVTN 084.

    Epitope mapping was performed 1 month after vaccination by IFN-γ ELISpot by deconvoluting responses to pools down to single 15-mer peptides. Responses to peptides overlapping by eight or more amino acids were counted as one epitope. Group 1 (immunized with Env) is shown in red; group 2 (immunized without Env) is shown in blue. (A) Number of targeted epitopes to Gag/Pol induced by vaccination. Colored lines represent means; black lines represent medians. (B) RCDF plot showing the proportion of participants on the y axis, with a response greater than or equal to the number of epitopes shown on the x axis. The dotted horizontal line separates nonresponders to the left (breadth 0) from responders targeting at least one epitope. Percentages in the key denote the proportion of responders.

  • Table 1 Baseline characteristics of the intent-to-treat population.

    Data are n (%) and median (range).

    Group 1: With
    Env (n = 50)
    Group 2:
    Without Env
    (n = 50)
    Total (N = 100)
    Sex
      Female43 (86%)39 (78%)82 (82%)
    Race/ethnicity
      White27 (54%)30 (60%)57 (57%)
      Black/African
    American
    2 (4%)2 (4%)4 (4%)
      Hispanic17 (34%)17 (34%)34 (34%)
      Asian3 (6%)0 (0%)3 (3%)
      Other1 (2%)1 (2%)2 (2%)
    Age (years)22 (18–48)21 (18–43)21 (18–48)

Supplementary Materials

  • stm.sciencemag.org/cgi/content/full/11/519/eaaw1673/DC1

    Fig. S1. Local and systemic reactogenicity.

    Fig. S2. Gag- and Pol-specific T cell responses in HVTN 084 1 month after vaccination in participants receiving rAd5 expressing Gag/Pol/Env (with Env) or Gag/Pol alone (without Env).

    Fig. S3. Rate and magnitude of T cell responses in HVTN 084 measured by IFN-γ ELISpot.

    Fig. S4. HLA types and targeted 15-mers for each participant.

    Fig. S5. Epitope breadth of Gag- and Pol-specific T cell responses in HVTN 084.

    Fig. S6. Example of the gating strategy for ICS for PBMCs from a HVTN 084 vaccine recipient.

  • This PDF file includes:

    • Fig. S1. Local and systemic reactogenicity.
    • Fig. S2. Gag- and Pol-specific T cell responses in HVTN 084 1 month after vaccination in participants receiving rAd5 expressing Gag/Pol/Env (with Env) or Gag/Pol alone (without Env).
    • Fig. S3. Rate and magnitude of T cell responses in HVTN 084 measured by IFN-γ ELISpot.
    • Fig. S4. HLA types and targeted 15-mers for each participant.
    • Fig. S5. Epitope breadth of Gag- and Pol-specific T cell responses in HVTN 084.
    • Fig. S6. Example of the gating strategy for ICS for PBMCs from a HVTN 084 vaccine recipient.

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