WorldCat Identities

Mcilroy, Dorian

Overview
Works: 4 works in 4 publications in 2 languages and 5 library holdings
Roles: Thesis advisor
Publication Timeline
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Most widely held works by Dorian Mcilroy
The Immune Response to the RT181-189 Epitope in HIV-1-Infected Patients is Associated with Viral Sequence Polymorphism Flanking the Epitope by Yovana Pacheco( )

1 edition published in 2011 in English and held by 2 WorldCat member libraries worldwide

Réponse immune cellulaire et thérapie de l'infection par le VIH by Yovana Pacheco Nieva( Book )

1 edition published in 2010 in French and held by 1 WorldCat member library worldwide

Pendant le traitement antirétroviral de l'infection par le VIH, différents cas d'échecs thérapeutiques peuvent survenir, dans ce travail nous nous sommes intéressés à deux aspects de cet échec: D'une part la grande variabilité du VIH permet au virus d'échapper aux médicaments antirétroviraux et peut être à l'origine d'un échec virologique. Il a été observé que plusieurs mutations de résistances sont localisées au sein des épitopes reconnus par les CTL, suggérant que la réponse immune peut avoir un effet sur les virus résistants. Afin d'étudier cette question, nous avons évalué, la réponse cytotoxique dirigée contre l'épitope RT181-189 chez 34 patients HLA-A2+ séropositif pour le VIH. Cet épitope comprend la mutation M184V, responsable de la résistance virale à la Lamivudine. Chez la majorité des patients en échec virologique sous Lamivudine la réponse contre cet épitope n'est pas présente alors qu'elle est fréquente chez les patients naïfs de traitement. Une étude détaillée sur les facteurs influençant le développement de la réponse à cet épitope a été effectuée. Par ailleurs, chez certains patients la reconstitution du compartiment CD4 n'est pas complète, il s'agit d'un échec immunologique. Dans ce cadre nous avons comparé les effets de trois cytokines (IL-2, IL-7, IL-15) et d'un agoniste de l'IL-15 RLI, sur les CD4+ et CD8+ des patients pour évaluer leur possible rôle thérapeutique dans la reconstitution de l'immunocompétence. Nos résultats montrent que la réponse proliférative des patients à l'IL-7 est préservée chez les patients VIH+ même chez ceux dont le taux de CD4 est faible. L'IL-15 et le RLI induisent une prolifération efficace de la population CD4 effecteur mémoire
Réponse immune cellulaire et thérapie de l'infection par le VIH by Yovana Pacheco Nieva( )

1 edition published in 2010 in French and held by 1 WorldCat member library worldwide

During HIV infection antiretroviral tritherapy efficiently inhibits viral replication and restores CD4 counts in infected patients. Nevertheless treatment failure may occur. In this work, we investigated two different aspects of this problem : Firstly, HIV sequence variability may provoke the emergence of resistant viruses leading to virological failure. The fact that many drug resistance mutations in HIV fall within CTL epitopes suggests that the immune response play a role in inhibiting resistant virus. In order to address this question we analyzed the response against the RT181-189 epitope covering the Lamivudine resistance mutation, M184V in 34 HLA-A2+ HIV+ infected patients. We found that RT181-189 is frequently recognized by ART Naive patients and poorly recognized by patients with virological failure under Lamivudine treatment. Both viral load and viral sequence polymorphism were associated with the presence of a CTL response against RT181-189. Secondly, some patients may undergo immunological failure; the recovery of CD4+ T-cell counts is incomplete despite complete suppression of viral replication. The aim of our study was to compare the effects of IL-2, IL-7, IL-15 and an agonist of IL-15, RLI, on CD4+ and CD8+ lymphocytes from HIV-infected patients, in order to evaluate the therapeutic potential of these molecules on immune reconstitution. Overall our results indicate that the proliferative response of CD4+ T-cells to IL-7 is preserved, even in patients with low CD4+ T-cell counts, and that both IL-15 and RLI can induce homeostatic proliferation of CD4+ effector-memory T-cells. In, RLI did not show greatly increased potency compared to native IL-15
Characterization of BKPyV-specific monoclonal antibodies in kidney transplant recipients after BKPyV reactivation by Ngoc khanh Nguyen( )

1 edition published in 2021 in English and held by 1 WorldCat member library worldwide

The BK polyomavirus (BKPyV) is ubiquitous and persists asymptomatically in the kidney. BKPyV reactivation can be seen in kidney transplant (KTx) recipients who receive immunosuppression treatments. The active replication can cause significant morbidity. Since no directly acting antiviral therapies are available, neutralizing antibodies represent possible therapeutics. The main objective of my PhD was, therefore, to generate neutralizing monoclonals with therapeutic potential. We also wanted to characterize the BKPyV-specific Bcell receptor (BCR) repertoire in KTx recipients with BKPyV reactivation. For that, we used fluorescence-labeled BKPyV virus-like particles (VLPs) to isolate a population of BKPyV-specific B cells. Using single-cell RNA seq technique, we obtained 2158 BKPyV-specific antibody sequences which were subsequently submitted to bioinformatic analysis. Our results show that the BCR repertoire was highly diverse in terms of both V-gene usage and clonotype diversity. The BKPyV-specific antibody response was dominated by IgM, then IgG. Although memory IgG and memory IgM B-cells were somatically hypermutated and expressed distinct BCR repertoires, the gene expression profile of these two B-cell subsets was highly similar. Furthermore, sequence-based clustering allowed us to identify a group of 41F17-like broadly neutralizing antibodies. After in vitro expression and characterization of more than 20 candidates, we found the antibody 120 representing a potent antibody for therapeutic purposes due to its stronger neutralizing antiviral activity compared to 41F17
 
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