Abstract
BackgroundExtra-cellular roles of Tat might be the main cause of maintenance of HIV-1 infected CD4 T cells or reservoir cells. We developed a synthetic vaccine based on a Tat variant of 101 residues called Tat Oyi, which was identified in HIV infected patients in Africa who did not progress to AIDS. We compared, using rabbits, different adjuvants authorized for human use to test on ELISA the recognition of Tat variants from the five main HIV-1 subtypes. A formulation was tested on macaques followed by a SHIV challenge with a European strain.ResultsTat Oyi with Montanide or Calcium Phosphate gave rabbit sera able to recognize all Tat variants. Five on seven Tat Oyi vaccinated macaques showed a better control of viremia compared to control macaques and an increase of CD8 T cells was observed only on Tat Oyi vaccinated macaques. Reservoir cells were not detectable at 56 days post-challenge in all Tat Oyi vaccinated macaques but not in the controls.ConclusionThe Tat Oyi vaccine should be efficient worldwide. No toxicity was observed on rabbits and macaques. We show in vivo that antibodies against Tat could restore the cellular immunity and make it possible the elimination of reservoir cells.
Highlights
Extra-cellular roles of Tat might be the main cause of maintenance of HIV-1 infected CD4 T cells or reservoir cells
Tat differs from other HIV-1 regulatory proteins because it is rapidly secreted by CD4+ T cells following HIV-1 infection, and extra-cellular Tat is suspected to be directly involved in the collapse of the cellular immune response against HIVinfected cells [2] and directly contributes to the pathology
Three adjuvants authorized for human use trigger an immune response with Tat Oyi similar to what was observed with the complete Freund adjuvant in a former study [22]
Summary
Extra-cellular roles of Tat might be the main cause of maintenance of HIV-1 infected CD4 T cells or reservoir cells. The HIV-1 Tat protein plays important roles in the virus life cycle and maintenance of HIV-1 infected CD4+ T cells [1,2]. It is a trans-activating regulatory protein that stimulates efficient transcription of the viral genome, which requires structural changes of Tat to bind to a RNA stemloop structure called TAR [3,4]. Tat differs from other HIV-1 regulatory proteins because it is rapidly secreted by CD4+ T cells following HIV-1 infection, and extra-cellular Tat is suspected to be directly involved in the collapse of the cellular immune response against HIVinfected cells [2] and directly contributes to the pathology (page number not for citation purposes). Further studies have emphasized the hypothesis that anti-Tat CTLs are important in controlling virus replication early after primary infection [14,15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
