Tat-Neutralizing Antibodies in Vaccinated Macaques

A synthetic HIV‐1 Tat protein breaches the skin barrier and elicits Tat‐neutralizing antibodies and cellular immunity

“…These results extend previous observations demonstrating the immunodominance of these epitopes after intranasal immunization [24,25] and suggest that sTat is processed and presented by epidermal Langerhans cells (LC) the same way as by the dendritic cells of the mucosal epithelium. These epitopes are generally conserved and play a critical role in the cellular uptake of Tat and transactivation [26][27][28][29]. Moreover, anti-Tat antibodies elicited after transcutaneous immunization neutralized Tat-driven transactivation, demonstrating the potential of this route to elicit antibodies that bind to extracellular Tat, which conceivably are capable of inhibiting its deleterious effects.…”

“…It is composed of 86-101 amino acid residues (depending on the isolate) encoded by two exons. The first 72 amino acid residues (encoded by the first exon) are organized into three functional domains: (i) an acidic N-terminal region (aa [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] that binds to cell surface CD26 and is thought to mediate immunosuppressive activity [3]; (ii) a cysteine-rich domain (aa [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] that mediates binding to chemokine receptors [4]; and (iii) the basic domain (aa 41-60). The latter domain is responsible for the internalization of extracellular Tat and its import into the nucleus and is also required for binding to short RNA transcripts containing the viral transactivation-responsive element (TAR) [5,6].…”

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

“…Indeed, the Tat protein of 86 aa from a clade B lab-adapted HIV-1 virus (HTLV-IIIB strain, clone BH-10) isolated more than 20 years ago [164] is very well recognized by sera from African individuals infected with different virus clades, including clade C, which is responsible for more than half of new HIV-1 infections worldwide [165], with similar prevalence and epitope mapping titers of anti-Tat antibodies [120]. Similarly, Tat proteins from different viral clades are cross-recognized by sera from HIV-1 seropositive individuals [166,167], and macaques immunized with a clade B recombinant Tat protein develop anti-Tat antibodies cross-reacting with HIV-1 Tat peptides from B and C clades [142].…”

“…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]. Similarly, immunization with Tat elicits antibody responses in rodents, monkeys, and humans able to block the activity of extracellular Tat on cellular entry, gene expression, and replication [4,84,[133][134][135][136][137][138][139][140][141][142]. Moreover, strong anti-Tat antibody responses correlated with an efficient reduction in plasma viremia and long-term protection in Tat protein-vaccinated monkeys challenged intrarectally with an heterologous SHIV virus [143].…”

“…Another important feature of Tat rendering it a relevant vaccine antigen is the conservation of its immunogenic regions among the HIV-1 M group at the sequence, functional, and conformational level [120,142,151,152,154,163]. Indeed, the Tat protein of 86 aa from a clade B lab-adapted HIV-1 virus (HTLV-IIIB strain, clone BH-10) isolated more than 20 years ago [164] is very well recognized by sera from African individuals infected with different virus clades, including clade C, which is responsible for more than half of new HIV-1 infections worldwide [165], with similar prevalence and epitope mapping titers of anti-Tat antibodies [120].…”