Specificity and effect on apoptosis of Tat antibodies from vaccinated and SHIV-infected rhesus macaques and HIV-infected individuals

Abstract

Recent contributions have demonstrated that actively secreted Tat protein plays an important functional role in human immunodeficiency virus-1 (HIV-1) infection and that Tat antibodies might interfere with disease progression by blocking the protein extracellularly. In this context we have studied the recognition of several Tat mutants as well as various synthetic Tat fragments by anti-Tat monoclonal antibodies and by IgG antibodies from a large collection of slow and fast-progressor infected individuals. We have also tested the sera from simian/human immunodeficiency virus (SHIV)-infected macaques with these Tat peptides. Important differences were found between long-term non-progressors and fast-progressors, and between human and monkey sera in terms of antibody specificity. Rabbits and macaques were immunised with several Tat peptides and we found that certain antibody subsets from immunised animals recognised the cognate protein Tat and had the capacity to inhibit Tat-induced apoptosis of T cells. Such antibodies might be important for controlling Tat-induced death in cells uninfected by HIV-1.

The binding affinity of double‐stranded RNA motifs to HIV‐1 Tat protein affects transactivation and the neutralizing capacity of anti‐Tat antibodies elicited after intranasal immunization

“…Both dsRNA motifs potentiated the anti-Tat antibody responses, which were comparable to those elicited in the presence of CT. Analysis of the fine-specificity of anti-Tat IgG antibodies using synthetic peptides revealed strong reactivity with peptides 1-20 and 44-61, which represent important epitopes [10,[19][20][21][22][31][32][33][34][35]. However, only sera of mice immunized with sTat and pI:pC motif inhibited Tat-driven transactivation.…”

“…The specificity of serum antibodies was determined using ELISA plates coated with peptides 1-20 and 44-61, which have been reported to represent critical neutralizing B cell epitopes of Tat protein [19][20][21][22] and have limited antigenic polymorphism among HIV-1 strains [23]. Although all tested sera reacted with both peptides (Fig.…”

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].…”

Recent Advances in the Development of HIV-1 Tat-Based Vaccines

“…Consistent with these data, other studies show that sera from macaques immunized with a recombinant Tat protein of clade B cross-react with HIV-1 Tat peptides from B and C clades, block the cellular uptake of extracellular Tat and neutralize its activity in transactivation assays [39,216]. Finally, other recent reports showed that anti-Tat sera from a large cohort of HIV-1 seropositive Caucasian individuals cross-react with Tat from different viral isolates, including HIV-1 subtype E, SHIV 89.6P and SIV mac251 [182], and that sera collected in France from HIV-infected individuals recognize equally well Tat proteins from distinct HIV strains of clades A, B and D [25]. These results indicate that the overall identity of Tat is preserved at the sequence, functional and conformational level and provide strong formal evidence that a Tat-based vaccine may indeed represent a universal anti-HIV tool capable of inducing immune responses effective against multiple virus clades.…”