Cell-Mediated Immune Predictors of Vaccine Effect on Viral Load and CD4 Count in a Phase 2 Therapeutic HIV-1 Vaccine Clinical Trial.
| Autor: | Huang Y; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, M2-C200, WA, USA; Department of Global Health, University of Washington, Seattle, WA, USA. Electronic address: yunda@scharp.org., Pantaleo G; Centre Hospitalier Universitaire Vaudois, Rue du Bugnon 46, BH10-527, CH-1011 Lausanne, Switzerland. Electronic address: Giuseppe.Pantaleo@chuv.ch., Tapia G; Centre Hospitalier Universitaire Vaudois, Rue du Bugnon 46, BH10-527, CH-1011 Lausanne, Switzerland. Electronic address: Gonzalo.Tapia@chuv.ch., Sanchez B; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, M2-C200, WA, USA. Electronic address: bprigmore@scharp.org., Zhang L; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, M2-C200, WA, USA. Electronic address: yzhang2@scharp.org., Trondsen M; Bionor Pharma AS, P.O. Box 1477 Vika, NO-0116 Oslo, Norway. Electronic address: monica.trondsen@gmail.com., Hovden AO; Bionor Pharma AS, P.O. Box 1477 Vika, NO-0116 Oslo, Norway. Electronic address: arntovehovden@gmail.com., Pollard R; University of California, Davis School of Medicine, 4150 V Street, Suite G500 PSSB, 95817 Sacramento, CA, USA. Electronic address: rbpollard@ucdavis.edu., Rockstroh J; Oberarzt an der Medizinischen Universitätsklinik, Innere-Rheuma-Tropen Ambulanz, Sigmund-Freud-Str. 25, 53105 Bonn, Venusberg, Germany. Electronic address: Juergen.Rockstroh@ukb.uni-bonn.de., Ökvist M; Bionor Pharma AS, P.O. Box 1477 Vika, NO-0116 Oslo, Norway. Electronic address: mo@bionorpharma.com., Sommerfelt MA; Bionor Pharma AS, P.O. Box 1477 Vika, NO-0116 Oslo, Norway. Electronic address: ms@bionorpharma.com. |
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| Jazyk: | angličtina |
| Zdroj: | EBioMedicine [EBioMedicine] 2017 Oct; Vol. 24, pp. 195-204. Date of Electronic Publication: 2017 Sep 22. |
| DOI: | 10.1016/j.ebiom.2017.09.028 |
| Abstrakt: | Background: In a placebo-controlled trial of the peptide-based therapeutic HIV-1 p24 Gag 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 log Findings: A lower fold-change of CD4+ T-cell proliferation was associated with VE CD4 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 VE VL at week 44 (p=0.047, q=0.07). A higher fold-change of TNF-α was associated with VE VL 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 VE VL at week 48 (p=0.017, q=0.036). TNF-α levels (>median) were associated with VE CD4 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. (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.) |
| Databáze: | MEDLINE |
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