Définition d’épitopes CTL dans l’ADN VIH-1 archivé et présentables par le HLA-B : perspective vaccinale

Abstract : Due to advances in antiretroviral therapy (ART), HIV-1 replication can nowadays be controlled among treated patients. Now, the objective is to find new therapeutic strategies to either eradicate the virus or achieve a “functional cure”. Therapeutic vaccines inducing cytotoxic T lymphocytes (CTL) are one of the most promising approaches. An effective vaccine must take into account the CTL epitopes variability in viral reservoirs and the human leukocytes antigen (HLA)-class I- allele-specific restriction. Using data from archived virus in HIV-1-infected patients from the Bordeaux University Hospital, we provide confirmation of important CTL epitope variability in HIV-1 proviral DNA, a major source contributing to viral rebound after stopping ART. We also found that mutations leading to this variability can affect the predicting MHC-I-epitope binding affinity and prevent their recognition. Moreover, we have identified highly conserved epitopes and epitopes carrying mutations with no significant effect on binding affinity, which are restricted by the most common HLA-B alleles in Caucasians and Africans. These epitopes could be used for the development of a multi-epitope-based peptide vaccine according to the genetics of patients.
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Master Thesis
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Submitted on : Wednesday, February 13, 2019 - 6:52:00 PM
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Marine Jourdain. Définition d’épitopes CTL dans l’ADN VIH-1 archivé et présentables par le HLA-B : perspective vaccinale. Sciences pharmaceutiques. 2018. ⟨dumas-02018388⟩

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