دورية أكاديمية
HIV-Tat immunization induces cross-clade neutralizing antibodies and CD4+ T cell increases in antiretroviral-treated South African volunteers: A randomized phase II clinical trial
| العنوان: | HIV-Tat immunization induces cross-clade neutralizing antibodies and CD4+ T cell increases in antiretroviral-treated South African volunteers: A randomized phase II clinical trial |
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| المؤلفون: | Ensoli, Barbara, Nchabeleng, Maphoshane, Ensoli, Fabrizio, Tripiciano, Antonella, Bellino, Stefania, Picconi, Orietta, Sgadari, Cecilia, Longo, Olimpia, Tavoschi, Lara, Joffe, Daniel, Cafaro, Aurelio, Francavilla, Vittorio, Moretti, Sonia, Pavone Cossut, Maria Rosaria, Collacchi, Barbara, Arancio, Angela, Paniccia, Giovanni, Casabianca, Anna, Magnani, Mauro, Buttò, Stefano, Levendal, Elise, Ndimande, John Velaphi, Asia, Bennett, Pillay, Yogan, Garaci, Enrico, Monini, Paolo |
| المساهمون: | Ensoli, Barbara, Nchabeleng, Maphoshane, Ensoli, Fabrizio, Tripiciano, Antonella, Bellino, Stefania, Picconi, Orietta, Sgadari, Cecilia, Longo, Olimpia, Tavoschi, Lara, Joffe, Daniel, Cafaro, Aurelio, Francavilla, Vittorio, Moretti, Sonia, Pavone Cossut, Maria Rosaria, Collacchi, Barbara, Arancio, Angela, Paniccia, Giovanni, Casabianca, Anna, Magnani, Mauro, Buttò, Stefano, Levendal, Elise, Ndimande, John Velaphi, Asia, Bennett, Pillay, Yogan, Garaci, Enrico, Monini, Paolo |
| سنة النشر: | 2016 |
| المجموعة: | ARPI - Archivio della Ricerca dell'Università di Pisa |
| مصطلحات موضوعية: | AIDS, CART, CD4+ T cell, Clinical trial, Cross-clade antibodie, HIV, Neutralization, Tat, Therapy intensification, Vaccine, AIDS Vaccine, Adolescent, Adult, Antibodies, Neutralizing, Antiretroviral Therapy, Highly Active, CD4-Positive T-Lymphocyte, Cross Reaction, Female, HIV Antibodie, HIV Infection, HIV-1, Human, Immunization Schedule, Immunogenicity, Male, Middle Aged, South Africa, Vaccination |
| الوصف: | Background: Although combined antiretroviral therapy (cART) has saved millions of lives, it is incapable of full immune reconstitution and virus eradication. The transactivator of transcription (Tat) protein is a key human immunodeficiency virus (HIV) virulence factor required for virus replication and transmission. Tat is expressed and released extracellularly by infected cells also under cART and in this form induces immune dysregulation, and promotes virus reactivation, entry and spreading. Of note, anti-Tat antibodies are rare in natural infection and, when present, correlate with asymptomatic state and reduced disease progression. This suggested that induction of anti-Tat antibodies represents a pathogenesis-driven intervention to block progression and to intensify cART. Indeed Tat-based vaccination was safe, immunogenic and capable of immune restoration in an open-label, randomized phase II clinical trial conducted in 168 cART-treated volunteers in Italy. To assess whether B-clade Tat immunization would be effective also in patients with different genetic background and infecting virus, a phase II trial was conducted in South Africa. Methods: The ISS T-003 was a 48-week randomised, double-blinded, placebo-controlled trial to evaluate immunogenicity (primary endpoint) and safety (secondary endpoint) of B-clade Tat (30 μg) given intradermally, three times at 4-week intervals, in 200 HIV-infected adults on effective cART (randomised 1:1) with CD4+ T-cell counts ≥200 cells/μL. Study outcomes also included cross-clade anti-Tat antibodies, neutralization, CD4+ T-cell counts and therapy compliance. Results: Immunization was safe and well-tolerated and induced durable, high titers anti-Tat B-clade antibodies in 97 % vaccinees. Anti-Tat antibodies were cross-clade (all vaccinees tested) and neutralized Tat-mediated entry of oligomeric B-clade and C-clade envelope in dendritic cells (24 participants tested). Anti-Tat antibody titers correlated positively with neutralization. Tat vaccination increased CD4+ T-cell ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/27277839; info:eu-repo/semantics/altIdentifier/wos/WOS:000377979100001; volume:13; issue:1; numberofpages:22; journal:RETROVIROLOGY; http://hdl.handle.net/11568/935298Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84975138831; https://retrovirology.biomedcentral.com/articles/10.1186/s12977-016-0261-1Test |
| DOI: | 10.1186/s12977-016-0261-1 |
| الإتاحة: | https://doi.org/10.1186/s12977-016-0261-1Test http://hdl.handle.net/11568/935298Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.ACEACA2A |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s12977-016-0261-1 |
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