Reservoir cells no longer detectable after a heterologous SHIV challenge with the synthetic HIV-1 Tat Oyi vaccine

BACKGROUND: Extra-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. RESULTS: Tat 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. CONCLUSION: The 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

What does the structure-function relationship of the HIV-1 Tat protein teach us about developing an AIDS vaccine?

The human immunodeficiency virus type 1 (HIV-1) trans-activator of transcription protein Tat is an important factor in viral pathogenesis. In addition to its function as the key trans-activator of viral transcription, Tat is also secreted by the infected cell and taken up by neighboring cells where it has an effect both on infected and uninfected cells. In this review we will focus on the relationship between the structure of the Tat protein and its function as a secreted factor. To this end we will summarize some of the exogenous functions of Tat that have been implicated in HIV-1 pathogenesis and the impact of structural variations and viral subtype variants of Tat on those functions. Finally, since in some patients the presence of Tat-specific antibodies or CTL frequencies are associated with slow or non-progression to AIDS, we will also discuss the role of Tat as a potential vaccine candidate, the advances made in this field, and the importance of using a Tat protein capable of eliciting a protective or therapeutic immune response to viral challenge

PREVENTION AND CONTROL OF ALGA BLOOM

[1] The present invention relates to new ribonucleic acid molecules, new polypeptides and new polypeptides, that may be of use in the biological control of algae blooms, in particular blooms of green algae such as from the genus Ulva

HIV Extracellular Tat: Myth or Reality?

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A reasonable hope to cure from HIV with the Tat Oyi vaccine: results and follow up of a double blinded randomized phase I/IIa clinical trial in France

International audienceWe know that it was possible to cure from HIV for at least one patient called the “Berlin patient”. Although the hematopoietic stem cell transplantation that saves him was not reproducible, his cure from HIV was well documented and shows that two steps are required. The first step is that the HIV DNA in peripheral blood becomes and stays undetectable. The second step is a significant decrease of antibodies against HIV-1 (never observed in HIV infected patients under successful cART) called retroseroconversion. BIOSANTECH was the sponsor of a phase I/II clinical trial carried out at Marseille on 48 HIV infected volunteers under cART with the Tat Oyi vaccine (Loret et al., Retrovirology 2016). These volunteers were randomized in double-blind method into four groups (n=12) and three intradermal injections were made with respectively for each group 0, 11, 33, or 99ug of a synthetic Tat Oyi protein in buffer without adjuvant at times designated by month 0 (M0), M1 and M2. The volunteers then underwent a one month cART interruption at M5. The vaccine reduces of 1.5 log copies/ml the HIV rebound median compare to the placebo group. Furthermore no increase of HIV infected cells was observed following cART interruption (p=0.001). A follow up of volunteers three years after vaccination shows that vaccinated volunteers who were HIV DNA undetectable at the end of the trial are still undetectable and the number of HIV DNA undetectable increased in all groups excepted in the placebo group (Fig 1). Preliminary results show that retroseroconversion begins in two volunteers

HIV Extracellular Tat: Myth or Reality?

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Protein from the Sea Anemone Anemonia viridis with an Anti-Angiogenic Activity

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