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Immunité et protection induites par un lentivecteur ADN innovant chez les modèles animaux de vaccination VIH-1.

Abstract : We recently developed an innovative prototype non-integrative lentivector DNA vaccine against HIV-1 /AIDS that we tested in pilot studies using animal models of HIV vaccine. We found that a single immunization with our prototype vaccine (CAL-SHIV-IN-) allowed the implementation of potent humoral and cellular responses in all immunized macaques. In addition, both types of responses persisted over a period of 74 weeks post-immunization in absence of antigenic boost. The characterization of the above revealed that vaccine specific T cell responses included polyfunctional CD4+ and CD8+ T cells against all antigens expressed by the vaccine. Detailed phenotypic and functional examinations of these cells showed that they were composed of effector (EM) and central memory (CM) T cells. More importantly they also contained a fraction of precursor memory T cells with high proliferative capacity (PHPC). Immune responses primed by our vaccine regiment correlated with protection in all vaccinated macaques (6/6). As expected our vaccine-induced immune responses did not prevent from infection acquisition but controlled the replication of the highly pathogenic and heterologous SIVmac251 challenge given as repeated low dose by the intrarectal mucosal route. All vaccinated animals (6/6) controlled their viremia to undetectable level using conventional PCR during at least 10 months post infection (end of the experiment). We further focused on PHPC responses associated with viral control and found that these cells vigorously proliferate upon ex vivo stimulation with specific antigens in presence of the homeostatic IL-7 and IL-15 cytokines. Proliferating antigen specific cells contained a type of stem cell-like memory T cells (TSCM). These latter (TSCM) might be a major asset in favor of our lentivector and vaccination strategy due to their high capacity for self-regeneration/maintenance in absence of antigen source.
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https://tel.archives-ouvertes.fr/tel-01685755
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Submitted on : Tuesday, January 16, 2018 - 4:47:06 PM
Last modification on : Friday, October 23, 2020 - 5:04:22 PM
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  • HAL Id : tel-01685755, version 1

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Maha Moussa. Immunité et protection induites par un lentivecteur ADN innovant chez les modèles animaux de vaccination VIH-1.. Médecine humaine et pathologie. Université Grenoble Alpes, 2015. Français. ⟨NNT : 2015GREAV029⟩. ⟨tel-01685755⟩

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