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UNRAVELING THE MECHANISMS REQUIRED FOR HIV VACCINE PROTECTION

As published today in PLoS ONE, by binding the Envelope protein present on virus particles, HIV Tat forms a new virus entry complex that favours the infection of cells present at the portals of virus entry (i.e. dendritic cells, macrophages). These cells represent also key HIV reservoirs that ensure the persistence of HIV in the host even under an "effective" antiretroviral treatment. By binding Env, Tat renders ineffective anti-Env antibodies at blocking virus entry in target cells. Thus, both anti-Tat and anti-Env antibodies are required for efficient HIV neutralization and should be both present to block HIV acquisition and spreading, but also the persistent infection and residual disease which is still present under antiretroviral therapy.

"This finding offers an explanation for the marginal protection of preventative vaccines tested so far and suggest novel vaccine approaches for HIV infection and AIDS" " says Prof. Enrico Garaci, the President of the Istituto Superiore di Sanità (ISS).

Based on this rationale, a phase I Tat/Env preventative vaccine trial is ongoing in Italy, while therapeutic immunization with Tat in HAART-treated patients (which already produce anti-Env antibodies) has been advanced to phase II clinical trials both in Italy (Ensoli et al., PLoS ONE 2010) and in South Africa http://www.hiv1tat-vaccines.info.

The work has been conducted by the laboratory of Dr. B. Ensoli, National AIDS Center, ISS in cooperation with scientists from San Gallicano Hospital in Rome, University of Ferrara, Florence, Urbino and Novartis and stems out from funding of the Italian Ministry of Health and the EU Commission.

PLoS ONE "HIV-1 Tat promotes integrin-mediated HIV transmission to dendritic cells by binding Env spikes and competes neutralization by anti-HIV antibodies".

Published 14-11-2012 in Highlights , last update 28-03-2014

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