Vaccination with Rev and Tat against AIDS

Long-term protection against SHIV89.6P replication in HIV-1 Tat vaccinated cynomolgus monkeys

“…Specifically, we found that small differences in Tat which can be detected only by analytical HPLC and by uptake by dendritic cells (and not by other assays), make important differences in the targeting and effects of Tat on dendritic cells which are key to initiate proper immune responses ( [32], and unpublished data). Further, our results are in agreement with reports from pre-clinical [39,69] and clinical [40,41] trials indicating that vaccination with Tat is safe, immunogenic and effective at controlling virus replication and disease progression in the monkey model. These data suggest that a native Tat protein or tat DNA should be included in future vaccine designs, particularly in prime-boost regimens.…”

“…Similar results of protection were reported in the SIV model with viral vectors (Semliki Forest Virus and Modified Vaccinia Ankara Virus) expressing the SIV-Tat and -Rev genes [39]. Of importance, injection of plasmid DNA coding for the HIV-1 regulatory genes Nef, Rev and Tat was reported to be safe and immunogenic in HIV-1 infected individuals [40,41].…”

Comparative study of Tat vaccine regimens in Mauritian cynomolgus and Indian rhesus macaques: Influence of Mauritian MHC haplotypes on susceptibility/resistance to SHIV89.6P infection

“…Tat combined with other HIV antigens might better confer protection at higher challenge doses. Immunizations with Tat plus Rev and Tat plus other nonstructural HIV gene products have shown protection against SIV [45,46]. A potential synergy between Tat and Env leading to enhanced protective efficacy in rhesus macaques against SHIV 89.6P was recently reported [44].…”

“…The significantly higher peak Tat-specific T cell proliferative responses seen in vaccinated macaques with the resistant haplotypes prior to challenge suggest cellular immunity should be further explored as a possible mechanism for the observed resistance. Results of the haplotype analysis and vaccine evaluations, together with reports showing that vaccines targeting Tat in combination with other viral proteins elicit good protective efficacy in non-human primates [44][45][46], suggest that HIV Tat vaccines might be best exploited in combination with other viral antigens.…”

Using death to one's advantage: HIV modulation of apoptosis

“…Several vaccine approaches for limiting HIV infection are currently underway and many include a Tat component in the vaccine. Vaccines in clinical and pre-clinical trials have included: (1) Tat expression vectors (both soluble and endogenous forms of Tat); 75,76 (2) as part of a multiple DNA expression plasmids encoding for several HIV genes; 77 (3) in live attenuated HIV vaccines; [78][79][80][81][82][83] and (4) in virus-like particles (VLPs) both in DNA expression vectors and as purified protein. 84 Therefore, a better comprehension of Tat-induced apoptosis and immunosuppressive mechanisms are important for new vaccine designs.…”