Literatura académica sobre el tema "Anticorps neutralisants à large spectre (AcNLS)"
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Artículos de revistas sobre el tema "Anticorps neutralisants à large spectre (AcNLS)"
Dalmat, Yann-Mickael. "Rémission d’infection à VIH : des anticorps neutralisants à large spectre contrôlent le virus". Option/Bio 34, n.º 679-680 (noviembre de 2023): 12. http://dx.doi.org/10.1016/s0992-5945(23)00352-5.
Texto completoTesis sobre el tema "Anticorps neutralisants à large spectre (AcNLS)"
Nemoz, Benjamin. "Exploration longitudinale à haut débit et en cellule unique du répertoire d'anticorps neutralisants à large spectre chez un neutraliseur d'élite du VIH-1". Electronic Thesis or Diss., Université Grenoble Alpes, 2024. http://www.theses.fr/2024GRALV012.
Texto completoHuman Immunodeficiency Virus type 1 (HIV-1) infection remains a major global health concern, with an estimated 37.7 million people living with the virus worldwide and new contaminations above a million cases yearly. Efficient anti-retroviral therapies are available, allowing a sustained relief for infected individuals. These therapeutics have also contributed to a better prevention and helped curb the epidemic, notably in high-income countries. However, a vaccine is still highly awaited for controlling this epidemic, especially in lower-income regions and precarious settings.The protective role of neutralizing antibodies (NAbs) has been unequivocally demonstrated in both animal models of HIV infection and in human settings. Consequently, the development of a B-cell-based vaccine capable of eliciting antibodies (Abs) with the ability to neutralize the majority of circulating viruses, namely broadly NAbs (bNAbs), could be foreseen as an answer to the HIV pandemic.The investigation of bNAb development in HIV-1 elite neutralizers provides valuable insights to inform the design of such vaccines. To date, most of the undertaken studies have relied on conventional single B-cell FACS sorting to isolate bNAbs. In the present study, we have used the Chromium Single Cell Immune Profiling approach to conduct a high-throughput longitudinal single-cell exploration of the B-cell repertoire in an HIV-1 elite neutralizer. Importantly, this novel method enables the use of a much greater number of HIV envelope glycoprotein (Env) baits compared to regular FACS-based Ab isolation studies, providing a more comprehensive view of the anti-Env Ab repertoire. In addition, this approach yields a wealth of information on the nature of the specific Abs identified and the corresponding B-cells.The study enabled the uncovering of the sequence of 12,130 putative HIV Env specific Abs. Antibodies from 39 lineages were produced and tested for neutralization, revealing 21 distinct neutralizing lineages. The results thus demonstrated the ability of the method to explore large antigen-specific Ab repertoires from longitudinal samples. The neutralizing activity of Abs from four neutralizing lineages together recapitulated the serum activity of the donor, achieving neutralization against 62.4 % of a large predictive panel of 126 pseudoviruses. One of these neutralizing Ab lineages was shown to target the gp120 high-mannose patch supersite with great breadth and potency; Abs from this lineage were sensitive to the presence of a glycan in position N332. A single of those Abs achieved most of the neutralization breadth (51.1 %) with a high potency (mean IC50 of 91.1 ng.mL-1). This Ab exhibited a 23 AA-long CDRH3 and 20 % somatic hypermutation (SMH). The lineage showed continuous evolution over 6.5 years of maturation, with observed SHM rates ranging from 2.0 % to 30.6 % for the heavy chain, without any insertions or deletions.Conventional FACS-based sorting was previously used to isolate bNAbs from the same donor. In comparison, the single cell high-throughput approach made possible the isolation of orders of magnitude more Abs. Furthermore, the newly isolated NAbs were overall more potent and broader than those isolated previously, indicating the superiority of the novel method in recovering neutralizing lineages. Ongoing structural studies will elucidate the epitopes responsible for the broad neutralization observed in this donor. Together, the findings may help the design of reverse vaccine approaches, which show promise in the development of an effective AIDS vaccine
Rousset, Claire. "Coévolution entre les glycoprotéines d'enveloppe du VIH et les anticorps neutralisants à large spectre ciblant la région du glycane N332". Thesis, Université Grenoble Alpes (ComUE), 2018. http://www.theses.fr/2018GREAV071/document.
Texto completoHIV has been the cause of the AIDS pandemic since the 1980s. With over a million new infections each year, a prophylactic vaccine is needed to stop the virus spread. Among vaccine strategies, the induction of broadly neutralizing antibodies is one of the most promising, as they could protect against infection by the huge genetic diversity of circulating HIV strains. To date, no immunogen has induced such antibodies, but they have been isolated from HIV infected people. Indeed, a small fraction of infected individuals eventually develops broadly neutralizing antibodies that target vulnerable and conserved sites of the envelope glycoprotein. The region of the high-mannose patch, centred around a glycan at position N332 of gp120, is the most frequently targeted, and is therefore attractive from a vaccination standpoint.In order to better understand how antibodies targeting the high-mannose patch develop, we studied a donor selected from the International AIDS Vaccine Initiative Protocol C cohort with exceptional serum neutralizing activity. We isolated two antibody lineages targeting the N332 region from this individual's blood cells, which we characterized for their neutralizing activity and mapped their epitope. We also mapped the paratope of an antibody lineage from another Protocol C donor, also targeting the N332 region. Our results show the great diversity of solutions to achieve broad neutralization against this region. Lineage studies, as we have undertaken, provide an understanding of how antibody-virus coevolution leads to the selection of broadly neutralizing antibodies. The ultimate goal is to use this knowledge to develop immunogens and immunization protocols, to induce specific antibody lineage and drive their evolution towards broad neutralization
Malbec, Marine. "La transmission de cellule à cellule du VIH-1 : rôle de la protéine Nef et effet inhibiteur des anticorps neutralisants à large spectre". Paris 7, 2013. http://www.theses.fr/2013PA077191.
Texto completoWe have studied two aspects of HIV-1 cell-to-cell transmission. First, we have investigated the role of Nef in HIV-1 replication and cell transfer. Second, we have examined the effect of a panel of broad neutralizing antibodies (bNAbs) on cell-to-cell transmission and studied the mechanisms involved. Nef is an HIV regulatory protein indispensable for replication and pathogenicity in vivo. Nef is known to down-regulate the surface expression of various cellular molecules, to increase virions infectivity and to affect cellular motility. We have shown that Nef facilitates HIV cell-to-cell transmission and that this function is conserved among lentiviruses. Nef increases levels of the virus structural Gag protein in the cell and promotes Gag localization to the plasma membrane. In the absence of Nef, viral material transferred to target cells is mostly immature. BNAbs are defined by their potency and their breadth, neutralizing a wide'panel of circulating viral strains from a variety of clades. The antiviral activity of these bNAbs is typically measured in cell free infection assay but little is know about their ability to block cell-associated transmission. By examining 15 bNAbs in collaboration with Michel Nussenzweig's group, we demonstrate that only a small subset efficiently prevent HIV cell-to-cell transmission. These bNAbs accumulate at the virological synapse, block the formation of conjugates and inhibit the transfer of viral material to target cells. Infection by cellular contact is likely the main mode of virus dissemination in vivo and the bNAbs identified in our study may represent candidates for therapeutic or prophylactic strategies
Niessl, Julia. "Modulation of HIV-specific T cell responses during standard antiretroviral treatment and immunotherapy". Thesis, 2020. http://hdl.handle.net/1866/24606.
Texto completoOnly a small fraction of individuals infected with the human immunodeficiency virus (HIV) develops effective immune responses able to control the virus. In most individuals, the virus escapes the antiviral immune response and HIV-specific CD8+ T cell responses become exhausted. Untreated progressive HIV infection also leads to alterations in HIV-specific CD4+ T cells. This includes increased expression of co-inhibitory receptors and skewing towards a T follicular helper cell (Tfh) signature. Antiretroviral therapy (ART) is highly effective in controlling the HIV viral load at undetectable levels in the plasma. However, ART does not represent a cure as the virus integrates into the genome of infected cells from where the virus rebounds once ART is stopped. This demonstrates that the HIV-specific T cell immunity is not restored. However, the changes that are introduced during progressive infection and that are maintained after viral suppression with ART are poorly known. Broadly neutralizing antibodies (bNAbs) represent a potential alternative to ART. In addition to virus neutralization and unlike ART, bNAbs to do not limit HIV antigen availability and can engage the immune system. bNAb administration elicited adaptive immune responses that were associated with long-lasting viral control in a simian animal model but this has not been established in HIV-infected individuals. In this thesis, we therefore proceeded to study the modulation of HIV-specific T cell responses during standard ART and after an immunotherapeutic intervention using bNAbs. The first objective was to better understand persistent modulation of HIV-specific CD4+ T cell responses in ART-treated individuals. Our results demonstrated the persistent expansion of HIV-specific Tfh cell responses with multiple phenotypic and functional features that differed from Tfh cells specific for comparative viral antigens (cytomegalovirus, hepatitis B virus). These features were induced during chronic untreated HIV infection, persisted during ART and correlated with the translation-competent HIV reservoir. This suggests that persistent HIV antigen expression, despite effective ART, maintains these altered immunological features specifically for Tfh responses. For the second objective, we characterized changes in the HIV-specific CD8+ and CD4+ T cell immunity after bNAb treatment and analytical treatment interruption (ATI). For this, we used samples obtained from participants enrolled in a clinical phase Ib study that received combined infusion of bNAbs 10-1074 and 3BNC117 and demonstrated prolonged viral suppression after ATI. In these individuals, we detected an increase of HIV-specific CD8+ and CD4+ T cell responses during ART interruption when compared to baseline. Increased T cell responses were due to both expansion of pre-existing responses and the emergence of responses to new epitopes. In contrast, HIV-specific T cell responses remained unchanged in ART-treated individuals who did not receive bNAb infusions. This suggests that bNAb treatment and ATI is associated with increased HIV-specific T cell immunity while viral suppression is maintained. Together our results contribute to a better understanding of HIV-specific T cell responses during ART and immunotherapy treatment. Our findings may help to develop more effective HIV treatment strategies to improve the host’s immune system so that HIV can be controlled without the need for ART.