The Presence of Anti‐Tat Antibodies Is Predictive of Long‐Term Nonprogression to AIDS or Severe Immunodeficiency: Findings in a Cohort of HIV‐1 Seroconverters

Abstract

The human immunodeficiency virus (HIV) type 1 Tat protein plays a key role in the life cycle of the virus and in pathogenesis and is highly conserved among HIV subtypes. On the basis of this and of safety, immunogenicity, and efficacy findings in monkeys, Tat is being tested as a vaccine in phase 1 trials. Here, we evaluated the incidence and risk of progression to advanced HIV disease by anti-Tat serostatus in a cohort of 252 HIV-1 seroconverters. The risk of progression was lower in the anti-Tat-positive subjects than in the anti-Tat-negative subjects. Progression was faster in the persistently anti-Tat-negative subjects than in the transiently anti-Tat-positive subjects, and no progression was observed in the persistently anti-Tat-positive subjects.

Culturing of human peripheral blood cells reveals unsuspected lymphocyte responses relevant to HIV disease

“…Gallo, Ensoli, and Zagury (11,(27)(28)(29), recognizing that antiTat antibody production is associated with improved survival in HIV disease, argue that Tat immunization may be effective for preventing or attenuating HIV infection. The unique HIV priming and support capabilities that our studies now demonstrate for Tat also support the idea that stimulating high-titer humoral immunity to Tat may be an important addition to vaccine strategies.…”

HIV-1 Tat-Based Vaccines: An Overview and Perspectives in the Field of HIV/AIDS Vaccine Development

“…Cross-sectional studies in 302 HIV-infected patients showed that anti-Tat antibodies are more frequent at the asymptomatic stage of infection compared with the symptomatic stage, whereas no differences were observed for antibodies directed against structural proteins [120]. Furthermore, a longitudinal study on the Italian cohort of 252 HIV-1 seroconverters indicates that the presence of anti-Tat antibodies strongly correlates with slower disease progression and no AIDS event occurred in persistent anti-Tat positive subjects [127]. In addition, evidence exists that natural IgM antibodies reacting with Tat may provide an early initial defense against the pathological effects of Tat after HIV infection and influence the course of AIDS progression [131,132].…”

“…4,63,67,84,85] and 46% of anti-Tat seropositive individuals were reported when anti-Tat ELISA were carried out with Tat variants specific for the subtype infecting patients [119]. High antibody titers directed against a broad spectrum of Tat functional domains neutralize the effects of extracellular Tat on virus replication and cell functions and play an important role in the control of the HIV infection and disease progression [105,[119][120][121][122][123][124][125][126][127][128][129][130]. Cross-sectional studies in 302 HIV-infected patients showed that anti-Tat antibodies are more frequent at the asymptomatic stage of infection compared with the symptomatic stage, whereas no differences were observed for antibodies directed against structural proteins [120].…”

Effects of different routes of administration on the immunogenicity of the Tat protein and a Tat-derived peptide

“…[5][6][7][8][9][10][11] Thus, the inclusion of Tat in preventive and therapeutic vaccines has been pursued by several groups showing promising results in nonhuman primates [12][13][14][15][16] and in phase I and II clinical trials. [16][17][18][19] However, the development of vaccines able to induce protective responses has to face some major challenges such as: i) the compliance requested for mass immunizations; ii) the induction of immune responses in mucosal tissues, which are the predominant sites of HIV acquisition; 20 and iii) the isotypes of antibodies elicited, which may influence the level of vaccine efficacy.…”