Cell-Mediated Immune Predictors of Vaccine Effect on Viral Load and CD4 Count in a Phase 2 Therapeutic HIV-1 Vaccine Clinical Trial

Yunda Huang, Giuseppe Pantaleo, Gonzalo Tapia, Brittany Sanchez, Lily Zhang, Monica Trondsen, Arnt Ove Hovden, Richard B Pollard, Jürgen Rockstroh, Mats Ökvist, Maja A. Sommerfelt

Research output: Contribution to journalArticle

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Abstract

Background: In a placebo-controlled trial of the peptide-based therapeutic HIV-1 p24Gag vaccine candidate Vacc-4x, participants on combination antiretroviral therapy (cART) received six immunizations over 18weeks, followed by analytical treatment interruption (ATI) between weeks 28 and 52. Cell-mediated immune responses were investigated as predictors of Vacc-4x effect (VE) on viral load (VL) and CD4 count during ATI. Methods: All analyses of week 28 responses and fold-changes relative to baseline considered per-protocol participants (Vacc-4x:placebo=72:32) resuming cART after week 40. Linear regression models with interaction tests were used. VE was estimated as the Vacc-4x-placebo difference in log10-transformed VL (VEVL) or CD4 count (VECD4). Findings: A lower fold-change of CD4+ T-cell proliferation was associated with VECD4 at week 48 (p =0.036, multiplicity adjusted q=0.036) and week 52 (p =0.040, q=0.080). A higher fold-change of IFN-γ in proliferation supernatants was associated with VEVL at week 44 (p =0.047, q=0.07). A higher fold-change of TNF-α was associated with VEVL at week 44 (p =0.045, q=0.070), week 48 (p =0.028, q=0.070), and week 52 (p =0.037, q=0.074). A higher fold-change of IL-6 was associated with VEVL at week 48 (p =0.017, q=0.036). TNF-α levels (>median) were associated with VECD4 at week 48 (p =0.009, q=0.009). Interpretation: These exploratory analyses highlight the potential value of investigating biomarkers in T-cell proliferation supernatants for VE in clinical studies.

Original languageEnglish (US)
JournalEBioMedicine
DOIs
StateAccepted/In press - 2017

Fingerprint

AIDS Vaccines
CD4 Lymphocyte Count
Viral Load
HIV-1
Vaccines
Clinical Trials
T-cells
Placebos
Cell proliferation
Linear Models
Therapeutics
Cell Proliferation
Immunization
T-Lymphocytes
Biomarkers
Linear regression
Vacc-4x
Interleukin-6
Peptides

Keywords

  • Analytical treatment interruption (ATI)
  • CD4
  • HIV
  • Immune predictors
  • Therapeutic vaccine
  • Viral load

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Cell-Mediated Immune Predictors of Vaccine Effect on Viral Load and CD4 Count in a Phase 2 Therapeutic HIV-1 Vaccine Clinical Trial. / Huang, Yunda; Pantaleo, Giuseppe; Tapia, Gonzalo; Sanchez, Brittany; Zhang, Lily; Trondsen, Monica; Hovden, Arnt Ove; Pollard, Richard B; Rockstroh, Jürgen; Ökvist, Mats; Sommerfelt, Maja A.

In: EBioMedicine, 2017.

Research output: Contribution to journalArticle

Huang, Y, Pantaleo, G, Tapia, G, Sanchez, B, Zhang, L, Trondsen, M, Hovden, AO, Pollard, RB, Rockstroh, J, Ökvist, M & Sommerfelt, MA 2017, 'Cell-Mediated Immune Predictors of Vaccine Effect on Viral Load and CD4 Count in a Phase 2 Therapeutic HIV-1 Vaccine Clinical Trial', EBioMedicine. https://doi.org/10.1016/j.ebiom.2017.09.028
Huang, Yunda ; Pantaleo, Giuseppe ; Tapia, Gonzalo ; Sanchez, Brittany ; Zhang, Lily ; Trondsen, Monica ; Hovden, Arnt Ove ; Pollard, Richard B ; Rockstroh, Jürgen ; Ökvist, Mats ; Sommerfelt, Maja A. / Cell-Mediated Immune Predictors of Vaccine Effect on Viral Load and CD4 Count in a Phase 2 Therapeutic HIV-1 Vaccine Clinical Trial. In: EBioMedicine. 2017.
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T1 - Cell-Mediated Immune Predictors of Vaccine Effect on Viral Load and CD4 Count in a Phase 2 Therapeutic HIV-1 Vaccine Clinical Trial

AU - Huang, Yunda

AU - Pantaleo, Giuseppe

AU - Tapia, Gonzalo

AU - Sanchez, Brittany

AU - Zhang, Lily

AU - Trondsen, Monica

AU - Hovden, Arnt Ove

AU - Pollard, Richard B

AU - Rockstroh, Jürgen

AU - Ökvist, Mats

AU - Sommerfelt, Maja A.

PY - 2017

Y1 - 2017

N2 - Background: In a placebo-controlled trial of the peptide-based therapeutic HIV-1 p24Gag vaccine candidate Vacc-4x, participants on combination antiretroviral therapy (cART) received six immunizations over 18weeks, followed by analytical treatment interruption (ATI) between weeks 28 and 52. Cell-mediated immune responses were investigated as predictors of Vacc-4x effect (VE) on viral load (VL) and CD4 count during ATI. Methods: All analyses of week 28 responses and fold-changes relative to baseline considered per-protocol participants (Vacc-4x:placebo=72:32) resuming cART after week 40. Linear regression models with interaction tests were used. VE was estimated as the Vacc-4x-placebo difference in log10-transformed VL (VEVL) or CD4 count (VECD4). Findings: A lower fold-change of CD4+ T-cell proliferation was associated with VECD4 at week 48 (p =0.036, multiplicity adjusted q=0.036) and week 52 (p =0.040, q=0.080). A higher fold-change of IFN-γ in proliferation supernatants was associated with VEVL at week 44 (p =0.047, q=0.07). A higher fold-change of TNF-α was associated with VEVL at week 44 (p =0.045, q=0.070), week 48 (p =0.028, q=0.070), and week 52 (p =0.037, q=0.074). A higher fold-change of IL-6 was associated with VEVL at week 48 (p =0.017, q=0.036). TNF-α levels (>median) were associated with VECD4 at week 48 (p =0.009, q=0.009). Interpretation: These exploratory analyses highlight the potential value of investigating biomarkers in T-cell proliferation supernatants for VE in clinical studies.

AB - Background: In a placebo-controlled trial of the peptide-based therapeutic HIV-1 p24Gag vaccine candidate Vacc-4x, participants on combination antiretroviral therapy (cART) received six immunizations over 18weeks, followed by analytical treatment interruption (ATI) between weeks 28 and 52. Cell-mediated immune responses were investigated as predictors of Vacc-4x effect (VE) on viral load (VL) and CD4 count during ATI. Methods: All analyses of week 28 responses and fold-changes relative to baseline considered per-protocol participants (Vacc-4x:placebo=72:32) resuming cART after week 40. Linear regression models with interaction tests were used. VE was estimated as the Vacc-4x-placebo difference in log10-transformed VL (VEVL) or CD4 count (VECD4). Findings: A lower fold-change of CD4+ T-cell proliferation was associated with VECD4 at week 48 (p =0.036, multiplicity adjusted q=0.036) and week 52 (p =0.040, q=0.080). A higher fold-change of IFN-γ in proliferation supernatants was associated with VEVL at week 44 (p =0.047, q=0.07). A higher fold-change of TNF-α was associated with VEVL at week 44 (p =0.045, q=0.070), week 48 (p =0.028, q=0.070), and week 52 (p =0.037, q=0.074). A higher fold-change of IL-6 was associated with VEVL at week 48 (p =0.017, q=0.036). TNF-α levels (>median) were associated with VECD4 at week 48 (p =0.009, q=0.009). Interpretation: These exploratory analyses highlight the potential value of investigating biomarkers in T-cell proliferation supernatants for VE in clinical studies.

KW - Analytical treatment interruption (ATI)

KW - CD4

KW - HIV

KW - Immune predictors

KW - Therapeutic vaccine

KW - Viral load

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DO - 10.1016/j.ebiom.2017.09.028

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