دورية أكاديمية
HIV-1 Tat immunization restores immune homeostasis and attacks the HAART-resistant blood HIV DNA : Results of a randomized phase II exploratory clinical trial
| العنوان: | HIV-1 Tat immunization restores immune homeostasis and attacks the HAART-resistant blood HIV DNA : Results of a randomized phase II exploratory clinical trial |
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| المؤلفون: | F. Ensoli, A. Cafaro, A. Casabianca, A. Tripiciano, S. Bellino, O. Longo, V. Francavilla, O. Picconi, C. Sgadari, S. Moretti, M. P. R. Cossut, A. Arancio, C. Orlandi, L. Sernicola, M. T. Maggiorella, G. Paniccia, C. Mussini, L. Sighinolfi, G. Palamara, A. Gori, G. Angarano, M. Di Pietro, V. S. Mercurio, F. Castelli, G. Di Perri, P. Monini, E. Garaci, B. Ensoli, A. Lazzarin, M. Galli, M. Magnani |
| المساهمون: | F. Ensoli, A. Cafaro, A. Casabianca, A. Tripiciano, S. Bellino, O. Longo, V. Francavilla, O. Picconi, C. Sgadari, S. Moretti, M.P.R. Cossut, A. Arancio, C. Orlandi, L. Sernicola, M.T. Maggiorella, G. Paniccia, C. Mussini, A. Lazzarin, L. Sighinolfi, G. Palamara, A. Gori, G. Angarano, M. Di Pietro, M. Galli, V.S. Mercurio, F. Castelli, G. Di Perri, P. Monini, M. Magnani, E. Garaci, B. Ensoli |
| بيانات النشر: | BioMed Central |
| سنة النشر: | 2015 |
| المجموعة: | The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| مصطلحات موضوعية: | Antibodie, CD38 + HLA-DR + /CD8 + T cell, HAART, HIV-1, Neutralization, Proviral DNA, Tat protein, Vaccine, AIDS Vaccine, Acquired Immunodeficiency Syndrome, Adult, Antibodies, Neutralizing, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Female, Follow-Up Studie, HIV Antibodie, Human, Immunoglobulin G, Immunoglobulin M, Italy, Leukocyte, Male, Middle Aged, Treatment Outcome, Young Adult, tat Gene Products, Human Immunodeficiency Viru |
| الوصف: | Background: The phase II multicenter, randomized, open label, therapeutic trial (ISS T-002, Clinicaltrials.gov NCT00751595) was aimed at evaluating the immunogenicity and the safety of the biologically active HIV-1 Tat protein administered at 7.5 or 30 μg, given 3 or 5 times monthly, and at exploring immunological and virological disease biomarkers. The study duration was 48 weeks, however, vaccinees were followed until the last enrolled subject reached the 48 weeks. Results: The vaccine was safe and well tolerated and induced anti-Tat Abs in most patients (79%), with the highest frequency and durability in the Tat 30 μg groups (89%) particularly when given 3 times (92%). Vaccination promoted a durable and significant restoration of T, B, natural killer (NK) cells, and CD4 + and CD8 + central memory subsets. Moreover, a significant reduction of blood proviral DNA was seen after week 72, particularly under PI-based regimens and with Tat 30 μg given 3 times (30 μg, 3x), reaching a predicted 70% decay after 3 years from vaccination with a half-life of 88 weeks. This decay was significantly associated with anti-Tat IgM and IgG Abs and neutralization of Tat-mediated entry of oligomeric Env in dendritic cells, which predicted HIV-1 DNA decay. Finally, the 30 μg, 3x group was the only one showing significant increases of NK cells and CD38 + HLA-DR + /CD8 + T cells, a phenotype associated with increased killing activity in elite controllers. Conclusions: Anti-Tat immune responses are needed to restore immune homeostasis and effective anti-viral responses capable of attacking the virus reservoir. Thus, Tat immunization represents a promising pathogenesis-driven intervention to intensify HAART efficacy. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/25924841; info:eu-repo/semantics/altIdentifier/wos/WOS:000353539300001; volume:12; issue:1; numberofpages:28; journal:RETROVIROLOGY; http://hdl.handle.net/2434/355164Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84928563445; http://www.retrovirology.com/homeTest/ |
| DOI: | 10.1186/s12977-015-0151-y |
| الإتاحة: | https://doi.org/10.1186/s12977-015-0151-yTest http://hdl.handle.net/2434/355164Test http://www.retrovirology.com/homeTest/ |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.3CEDA138 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s12977-015-0151-y |
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