UNAIDS/WHO estimates that about 33 million people are living today with human immunodeficiency virus (HIV/AIDS) infection and, notably, Sub-Saharan Africa and Asia remain the regions most devastated by HIV/AIDS and are characterized by continuously increasing rates of infection (

Although the use of antiretroviral drugs (highly active antiretroviral therapy, HAART) has had a dramatically beneficial impact on HIV-infected individuals, its use in developing countries is still limited due to its cost and difficulties it poses to public health organizations. In addition, although effective in suppressing viral replication and blocking disease progression, HAART is largely ineffective in reducing chronic immune activation and immune dysregulation. Finally, not all patients under HAART, even if the therapy is keeping the virus suppressed and undetectable, experience an effective increase of CD4+ T cells, a biomarker of drug efficacy.

Therefore, the development of effective, safe, inexpensive, and easily administrable HIV vaccines remains one of the highest priorities of the world agenda for health, since it represents the only realistic way to control the global expansion of the HIV pandemic, especially in the developing world (

Tat-based HIV vaccines

VAXXIT aims to address the need for effective, safe, inexpensive, and easily administrable HIV vaccines with TatImmuneTM and PreVaxTatTM, two vaccines based on the HIV-1 Tat protein.

The Tat protein is the long arm of the HIV-1 tat regulatory gene that has a fundamental function in HIV infection, pathogenesis and disease. In the absence of Tat, the virus does not replicate and is not capable to infect new cells once it has infected the host cell. Tat is produced very early after the first infection, even before the virus integrates with (becomes part of) the host cell's genetic machinery and abundantly after, during active infection. After release by acutely infected cells in the extracellular matrix, its role in pathogenesis and disease progression is to clear the ground for the virus to infect new cells by recruiting, engaging, and activating uninfected cells. Thus, Tat is a key weapon in the virus hands to spread the HIV infection throughout the body.

Tat is, hence, an excellent target for HIV vaccine research: has a key role in helping the virus spread the infection and, in contrast to all other HIV proteins, anti-Tat antibodies not only are seldom found in HIV-infected people, and, when present, correlate with non-progression to full AIDS disease. Moreover, since Tat is well conserved across HIV virus forms in different parts of the world (clades), Tat-based vaccines will be suitable for use in most part of the world.

For more information on the Tat protein, visit the sections "A novel approach to vaccination" on

TatImmuneTM, a therapeutic HIV vaccine for HAART treated HIV patients

TatImmuneTM is a clinical phase vaccine candidate containing the recombinant subunit Tat protein in a biologically active form as the vaccine antigen. TatImmuneTM has shown efficacy in counteracting the chronic immune activation and the immune dysregulation in virologically suppressed HAART-treated patients, and in restoring functionality of their immune system. In this respect TatImmuneTM addresses the unmet need of HAART therapy.

The above results have been demonstrated in a randomized, open-label, phase II therapeutic clinical trial, conducted in 11 clinical centers in Italy
( ).

A second Phase II randomized, double-blinded, placebo-controlled, therapeutic trial in 200 ARV-treated individuals has initiated in South Africa (SA).

PreVaxTatTM, a preventative HIV vaccine

PreVaxTatTM is a vaccine candidate based on the combination the two HIV antigens, Tat and Env.

Mucosal (nasal) vaccination with Tat & Env proteins combined has been shown, in monkey studies, to prevent the spread of the virus from the site of the primary infection to regional lymph nodes and, consequently, to impede virus dissemination and the establishment of virus reservoirs in HIV target cells.

These data, that have inspired the new vaccine development strategies behind TatImmuneTM , the therapeutic vaccine, and PreVaxTatTM , the preventative vaccine, indicate that both anti-Tat and anti-Env antibodies are required to prevent or block HIV acquisition and spreading in healthy people. PreVaxTatTM addresses this need.

PreVaxTatTM is currently being tested in a clinical phase I study (safety and immunogenicity) in 3 clinical centers in Italy.

Intellectual Property Rights

VAXXIT owns the intellectual property rights (IPR) to the use of TatImmuneTM in HAART-treated patients.

IPR to the Tat vaccines patent estate are owned by Istituto Superiore di Sanità ( ), the Italian National Institute of Health.