Cell-Mediated Immune Predictors of Vaccine Effect on Viral Load and CD4 Count in a Phase 2 Therapeutic HIV-1 Vaccine Clinical Trial
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 18 weeks, followed by analytical treatment interruption (ATI) between weeks 28 and 52. Cell-med...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-10-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396417303821 |
| _version_ | 1818129277082664960 |
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| author | Yunda Huang Giuseppe Pantaleo Gonzalo Tapia Brittany Sanchez Lily Zhang Monica Trondsen Arnt-Ove Hovden Richard Pollard Jürgen Rockstroh Mats Ökvist Maja A. Sommerfelt |
| author_facet | Yunda Huang Giuseppe Pantaleo Gonzalo Tapia Brittany Sanchez Lily Zhang Monica Trondsen Arnt-Ove Hovden Richard Pollard Jürgen Rockstroh Mats Ökvist Maja A. Sommerfelt |
| author_sort | Yunda Huang |
| collection | DOAJ |
| description | 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 18 weeks, 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. |
| first_indexed | 2024-12-11T07:46:35Z |
| format | Article |
| id | doaj.art-fc8f494e48c9497d8de11cf5cf214668 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-11T07:46:35Z |
| publishDate | 2017-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-fc8f494e48c9497d8de11cf5cf2146682022-12-22T01:15:27ZengElsevierEBioMedicine2352-39642017-10-0124C19520410.1016/j.ebiom.2017.09.028Cell-Mediated Immune Predictors of Vaccine Effect on Viral Load and CD4 Count in a Phase 2 Therapeutic HIV-1 Vaccine Clinical TrialYunda Huang0Giuseppe Pantaleo1Gonzalo Tapia2Brittany Sanchez3Lily Zhang4Monica Trondsen5Arnt-Ove Hovden6Richard Pollard7Jürgen Rockstroh8Mats Ökvist9Maja A. Sommerfelt10Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, M2-C200, WA, USACentre Hospitalier Universitaire Vaudois, Rue du Bugnon 46, BH10-527, CH-1011 Lausanne, SwitzerlandCentre Hospitalier Universitaire Vaudois, Rue du Bugnon 46, BH10-527, CH-1011 Lausanne, SwitzerlandVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, M2-C200, WA, USAVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, M2-C200, WA, USABionor Pharma AS, P.O. Box 1477 Vika, NO-0116 Oslo, NorwayBionor Pharma AS, P.O. Box 1477 Vika, NO-0116 Oslo, NorwayUniversity of California, Davis School of Medicine, 4150 V Street, Suite G500 PSSB, 95817 Sacramento, CA, USAOberarzt an der Medizinischen Universitätsklinik, Innere-Rheuma-Tropen Ambulanz, Sigmund-Freud-Str. 25, 53105 Bonn, Venusberg, GermanyBionor Pharma AS, P.O. Box 1477 Vika, NO-0116 Oslo, NorwayBionor Pharma AS, P.O. Box 1477 Vika, NO-0116 Oslo, NorwayBackground: 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 18 weeks, 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.http://www.sciencedirect.com/science/article/pii/S2352396417303821Analytical treatment interruption (ATI)HIVTherapeutic vaccineViral loadImmune predictorsCD4 |
| spellingShingle | Yunda Huang Giuseppe Pantaleo Gonzalo Tapia Brittany Sanchez Lily Zhang Monica Trondsen Arnt-Ove Hovden Richard Pollard Jürgen Rockstroh Mats Ökvist Maja A. Sommerfelt Cell-Mediated Immune Predictors of Vaccine Effect on Viral Load and CD4 Count in a Phase 2 Therapeutic HIV-1 Vaccine Clinical Trial EBioMedicine Analytical treatment interruption (ATI) HIV Therapeutic vaccine Viral load Immune predictors CD4 |
| title | Cell-Mediated Immune Predictors of Vaccine Effect on Viral Load and CD4 Count in a Phase 2 Therapeutic HIV-1 Vaccine Clinical Trial |
| title_full | Cell-Mediated Immune Predictors of Vaccine Effect on Viral Load and CD4 Count in a Phase 2 Therapeutic HIV-1 Vaccine Clinical Trial |
| title_fullStr | Cell-Mediated Immune Predictors of Vaccine Effect on Viral Load and CD4 Count in a Phase 2 Therapeutic HIV-1 Vaccine Clinical Trial |
| title_full_unstemmed | Cell-Mediated Immune Predictors of Vaccine Effect on Viral Load and CD4 Count in a Phase 2 Therapeutic HIV-1 Vaccine Clinical Trial |
| title_short | Cell-Mediated Immune Predictors of Vaccine Effect on Viral Load and CD4 Count in a Phase 2 Therapeutic HIV-1 Vaccine Clinical Trial |
| title_sort | cell mediated immune predictors of vaccine effect on viral load and cd4 count in a phase 2 therapeutic hiv 1 vaccine clinical trial |
| topic | Analytical treatment interruption (ATI) HIV Therapeutic vaccine Viral load Immune predictors CD4 |
| url | http://www.sciencedirect.com/science/article/pii/S2352396417303821 |
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