Sequence Conservation and Antibody Cross‐Recognition of Clade B Human Immunodeficiency Virus (HIV) Type 1 Tat Protein in HIV‐1–Infected Italians, Ugandans, and South Africans

Abstract

We determined immune cross-recognition and the degree of Tat conservation in patients infected by local human immunodeficiency virus (HIV) type 1 strains. The data indicated a similar prevalence of total and epitope-specific anti-Tat IgG in 578 serum samples from HIV-infected Italian (n=302), Ugandan (n=139), and South African (n=137) subjects, using the same B clade Tat protein that is being used in vaccine trials. In particular, anti-Tat antibodies were detected in 13.2%, 10.8%, and 13.9% of HIV-1-infected individuals from Italy, Uganda, and South Africa, respectively. Sequence analysis results indicated a high similarity of Tat from the different circulating viruses with BH-10 Tat, particularly in the 1-58 amino acid region, which contains most of the immunogenic epitopes. These data indicate an effective cross-recognition of a B-clade laboratory strain-derived Tat protein vaccine by individuals infected with different local viruses, owing to the high similarity of Tat epitopes.

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

“…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].…”

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

“…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].…”

“…Extracellular Tat exerts a variety of biological activities that disable the immune system and permit the propagation of the virus [9]. Since Tat shows little variability among different HIV subtypes, particularly in the functional regions encoded by the first exon [10], the use of full-length Tat protein could be advantageous for therapeutic intervention. The immune system is likely to target its response to these domains, thereby preventing both Tat's extracellular action and Tat-driven transactivation inhibiting the immunosuppressive and neurotoxic properties of the protein.…”

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

“…It has been recently shown that antibodies directed against the N-terminus region of Tat, which is the most immunogenic in terms of humoral responses, 32,33 protect monkeys from infection acquisition, 15 suggesting that the Tat 1-20 peptide constitutes an interesting candidate for a preventive vaccine. To assess how different routes of administration may affect humoral immunogenicity of peptide vaccines, mice were vaccinated 3 times (at days 1, 14 and 28), by ID or OM route, with Tat 1-20 peptide (EPVDPRLEPWKHPGSQPKT, synthesized by solid phase method and purified by HPLC to >98% purity by UF Peptides, University of Ferrara, Italy), encompassing an immunodominant Tat epitope, 32,33 at the dose of 7mg.…”

“…To assess how different routes of administration may affect humoral immunogenicity of peptide vaccines, mice were vaccinated 3 times (at days 1, 14 and 28), by ID or OM route, with Tat 1-20 peptide (EPVDPRLEPWKHPGSQPKT, synthesized by solid phase method and purified by HPLC to >98% purity by UF Peptides, University of Ferrara, Italy), encompassing an immunodominant Tat epitope, 32,33 at the dose of 7mg. This dose contains the same number of molecules of 30mg of Tat protein.…”