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Review

Anti-Tat Immunity in HIV-1 Infection: Effects of Naturally Occurring and Vaccine-Induced Antibodies Against Tat on the Course of the Disease

National HIV/AIDS Research Center, Istituto Superiore di Sanità, Rome 00161, Italy
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Vaccines 2019, 7(3), 99; https://doi.org/10.3390/vaccines7030099
Received: 16 July 2019 / Revised: 8 August 2019 / Accepted: 15 August 2019 / Published: 26 August 2019
(This article belongs to the Special Issue Advances in Antibody-based HIV-1 Vaccine Development)
HIV-1 Tat is an essential protein in the virus life cycle, which is required for virus gene expression and replication. Most Tat that is produced during infection is released extracellularly and it plays a key role in HIV pathogenesis, including residual disease upon combination antiretroviral therapy (cART). Here, we review epidemiological and experimental evidence showing that antibodies against HIV-1 Tat, infrequently occurring in natural infection, play a protective role against disease progression, and that vaccine targeting Tat can intensify cART. In fact, Tat vaccination of subjects on suppressive cART in Italy and South Africa promoted immune restoration, including CD4+ T-cell increase in low immunological responders, and a reduction of proviral DNA even after six years of cART, when both CD4+ T-cell gain and DNA decay have reached a plateau. Of note, DNA decay was predicted by the neutralization of Tat-mediated entry of Env into dendritic cells by anti-Tat antibodies, which were cross-clade binding and neutralizing. Anti-Tat cellular immunity also contributed to the DNA decay. Based on these data, we propose the Tat therapeutic vaccine as a pathogenesis-driven intervention that effectively intensifies cART and it may lead to a functional cure, providing new perspectives and opportunities also for prevention and virus eradication strategies. View Full-Text
Keywords: HIV-1 Tat; anti-Tat antibodies; natural vs. vaccine-induced antibody response; crossclade antibodies; HIV-1 vaccine development; HIV-1 Tat therapeutic vaccine; HIV reservoir; cART intensification; functional cure; perspective for clinical implications HIV-1 Tat; anti-Tat antibodies; natural vs. vaccine-induced antibody response; crossclade antibodies; HIV-1 vaccine development; HIV-1 Tat therapeutic vaccine; HIV reservoir; cART intensification; functional cure; perspective for clinical implications
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MDPI and ACS Style

Cafaro, A.; Tripiciano, A.; Picconi, O.; Sgadari, C.; Moretti, S.; Buttò, S.; Monini, P.; Ensoli, B. Anti-Tat Immunity in HIV-1 Infection: Effects of Naturally Occurring and Vaccine-Induced Antibodies Against Tat on the Course of the Disease. Vaccines 2019, 7, 99. https://doi.org/10.3390/vaccines7030099

AMA Style

Cafaro A, Tripiciano A, Picconi O, Sgadari C, Moretti S, Buttò S, Monini P, Ensoli B. Anti-Tat Immunity in HIV-1 Infection: Effects of Naturally Occurring and Vaccine-Induced Antibodies Against Tat on the Course of the Disease. Vaccines. 2019; 7(3):99. https://doi.org/10.3390/vaccines7030099

Chicago/Turabian Style

Cafaro, Aurelio, Antonella Tripiciano, Orietta Picconi, Cecilia Sgadari, Sonia Moretti, Stefano Buttò, Paolo Monini, and Barbara Ensoli. 2019. "Anti-Tat Immunity in HIV-1 Infection: Effects of Naturally Occurring and Vaccine-Induced Antibodies Against Tat on the Course of the Disease" Vaccines 7, no. 3: 99. https://doi.org/10.3390/vaccines7030099

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