Parallel Conduction of the Phase I Preventive and Therapeutic Trials Based on the Tat Vaccine Candidate

被引:31
作者
Bellino, S. [1 ]
Francavilla, V. [1 ]
Longo, O. [1 ]
Tripiciano, A. [1 ]
Paniccia, G. [1 ]
Arancio, A. [2 ]
Fiorelli, V. [1 ]
Scoglio, A. [1 ]
Collacchi, B. [1 ]
Campagna, M. [2 ]
Lazzarin, A. [3 ]
Tambussi, G. [3 ]
Din, C. Tassan [3 ]
Visintini, R. [3 ]
Narciso, P. [4 ]
Antinori, A. [4 ]
D'Offizi, G. [4 ]
Giulianelli, M. [4 ]
Carta, M. [5 ]
Di Carlo, A. [2 ]
Palamara, G. [2 ]
Giuliani, M. [2 ]
Laguardia, M. E. [6 ]
Monini, P. [1 ]
Magnani, M. [6 ]
Ensoli, F. [2 ]
Ensoli, B. [1 ]
机构
[1] Natl AIDS Ctr, Ist Superiore Sanita, Viale Regina Elena 299, I-00161 Rome, Italy
[2] San Gallicano Hosp, Rome, Italy
[3] Osped San Raffaele, Milan, Italy
[4] Natl Inst Infect Dis L Spallanzani, Rome, Italy
[5] Univ Roma La Sapienza, Rome, Italy
[6] Univ Urbino, Urbino, Italy
关键词
HIV-Tat; vaccination; antibodies; safety; clinical trials;
D O I
10.2174/157488709789957529
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The native HIV-1 Tat protein was chosen as vaccine candidate for phase I clinical trials in both uninfected (ClinicalTrials.gov identifier: NCT00529698) and infected volunteers (ClinicalTrials.gov identifier: NCT00505401). The rationale was based on the role of Tat in the natural infection and AIDS pathogenesis, on the association of Tat-specific immune responses with the asymptomatic stage and slow-progression rate as well as on its sequence conservation among HIV clades (http://www.hiv1tat-vaccines.info/). The parallel conduction in the same clinical centers of randomized, double blind, placebo-controlled phase I studies both in healthy, immunologically competent adults and in HIV-infected, clinically asymptomatic, individuals represents a unique occasion to compare the vaccine-induced immune response in both the preventive and therapeutic setting. In both studies, the same lot of the native Tat protein was administered 5 times, every four weeks, subcute (SC) with alum adjuvant or intradermic (ID), in the absence of adjuvant, at 7.5 mu g, 15 mu g or 30 mu g doses, respectively. The primary and secondary endpoints of these studies were the safety and immunogenicity of the vaccine candidate, respectively. The study lasted 52 weeks and monitoring was conducted for on additional 3 years. The results of both studies indicated that the Tat vaccine is safe and well tolerated both locally and systemically and it is highly immunogenic at all the dosages and by both routes of administration. Vaccination with Tat induced a balanced immune response in uninfected and infected individuals. In particular, therapeutic immunization induced functional antibodies and partially reverted the marked Th1 polarization of anti-Tat immunity seen in natural infection, and elicited a more balanced Th1/Th2 immune response. Further, the number of CD4 T cells correlated positively with anti-Tat antibody titers. Based on these results, a phase II study is ongoing in infected drug-treated individuals (http://www.hiv1tat-vaccines.info/).
引用
收藏
页码:195 / 204
页数:10
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