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.

Ensoli, F., Cafaro, A., Casabianca, A., Tripiciano, A., Bellino, S., Longo, O., et al. (2015). HIV-1 Tat immunization restores immune homeostasis and attacks the HAART-resistant blood HIV DNA: Results of a randomized phase II exploratory clinical trial. RETROVIROLOGY, 12(1), 33 [10.1186/s12977-015-0151-y].

HIV-1 Tat immunization restores immune homeostasis and attacks the HAART-resistant blood HIV DNA: Results of a randomized phase II exploratory clinical trial

GORI, ANDREA;
2015

Abstract

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.
Articolo in rivista - Articolo scientifico
Antibodies; CD38<sup>+</sup>HLA-DR<sup>+</sup>/CD8<sup>+</sup> T cells; HAART; HIV-1; Neutralization; Proviral DNA; Tat protein; Vaccine; Virology; Infectious Diseases
English
33
Ensoli, F., Cafaro, A., Casabianca, A., Tripiciano, A., Bellino, S., Longo, O., et al. (2015). HIV-1 Tat immunization restores immune homeostasis and attacks the HAART-resistant blood HIV DNA: Results of a randomized phase II exploratory clinical trial. RETROVIROLOGY, 12(1), 33 [10.1186/s12977-015-0151-y].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/96643
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