Browsing by Subject "SIV"

Now showing 1 - 3 of 3
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    16S Intestinal Microbiome Sequences of Rhesus Macaques Treated with Chronic Morphine for 92 Days, SIV for 21 Days, or in Combination (Morphine for 70 Days then SIV+Morphine for 21 Days)
    (2017-04-10) Sindberg, Gregory M; Roy, Sabita; sind0017@umn.edu; Sindberg, Gregory M
    Rhesus Macaque fecal matter was sequenced at different intervals after receiving Morphine I.V., SIV infection, or in sequence. The intervals are as follows: Morphine for 92 days, SIV for 21 days, or a sequence of morphine for 70 days then SIV+Morphine for 21 days. This was used to look for microbial and metabolic changes due to the treatments.
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    Anti-CAR antibody response in SIV infected rhesus macaques
    (2022-11-28) Davey, Brianna, C; Pampusch, Mary, S; Cartwright, Emily, K; Abdelaal, Hadia, M; Rakasz, Eva, G; Rendahl, Aaron; Berger, Edward, A; Skinner, Pamela, J; skinn002@umn.edu; Skinner, Pamela, J; Skinner laboratory
    T cells expressing a simian immunodeficiency (SIV)-specific chimeric antigen receptor (CAR) and the follicular homing molecule, CXCR5, were infused into antiretroviral therapy (ART) suppressed, SIV-infected rhesus macaques to assess their ability to localize to the lymphoid follicle and control the virus upon ART interruption. The cells did not persist in the animals beyond 28 days. Development of anti-CAR antibodies could be responsible for the lack of persistence. Potential antigenic sites on the anti-SIV CAR used in these studies included domains 1 and 2 of CD4, the carbohydrate recognition domain (CRD) of mannose-binding lectin (MBL), and an extracellular domain of the costimulatory molecule, CD28, along with short linker sequences. Using a flow cytometry based assay and target cells expressing the CAR/CXCR5 construct, we examined the serum of the CAR T-cell treated animals to determine that the animals had developed an anti-CAR antibody response after infusion. Binding sites for the anti-CAR antibodies were identified by using alternative CARs transduced into target cells and by preincubation of the target cells with a CD4 blocking antibody. All of the treated animals developed antibodies in their serum that bound to CAR-T cells and the majority were capable of inducing an ADCC response. The CD4 antibody-blocking assay suggests that the dominant immunogenic components of this CAR are the CD4 domains with a possible additional site of the CD28 domain with its linker.
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    Correlates of cytotoxic T lymphocyte vaccine-induced control against Simian immunodeficiency virus (SIV)
    (2018-10) Mohammad, Hadia
    There is an urgent need to develop a successful HIV vaccine. Despite continuous efforts, development of a protective HIV-1 vaccine remains a big challenge. HIV-1/SIV-specific CD8+ T cells play a pivotal role in the control of virus replication. During chronic HIV-1 and SIV infections, virus replication is most concentrated within lymphoid B cell follicles, whereas virus-specific CD8+T cells concentrate in extrafollicular areas of secondary lymphoid tissues and tend to be excluded from follicular areas. My thesis focuses on identifying immune correlates of control associated with successful CD8+T cell-based SIV vaccines to help understand what is required to develop a successful HIV vaccine. My central hypothesis is that vaccine-induced control will be associated with induction of an early SIV-specific CD8+T cell response at the portal of viral entry and in lymphoid tissues and also with induction of high levels of virus-specific CD8+T cells in follicular areas of lymphoid tissues. I determined the location, abundance, and phenotype of virus-specific CD8+T cells and the abundance of virus-infected cells in vaccinated and unvaccinated rhesus macaques. Freshly collected unfixed tissue samples were analyzed using in situ tetramer staining combined with immunohistochemistry, in situ hybridization, confocal imaging, and quantitative image analysis. I found that vaccine-induced control was associated with induction of virus-specific CD8+T cells before challenge with pathogenic SIV. Virus-specific CD8+T cells expanded rapidly after challenge and resulted in high effector (SIV-specific CD8+T cells) to target (SIV-infected cells) ratios at the portal of viral entry and in lymph nodes. Additionally, vaccine-induced control correlated with the induction of high follicular: extrafollicular ratio of virus-specific CD8+T cells in lymphoid tissues. Moreover, this control correlated with induction of SIV-specific CD8+T cells that expressed little perforin and with SIV-specific CD8+ T cells in which perforin was exclusively localized to the cell membrane in lymphoid tissues. These cells are likely effector memory T cells with an immediate killing ability. These findings provide a better understanding of the immune correlates of CD8+T cell-based vaccine-induced control against SIV and provide understating of what is needed to create an effective HIV vaccine.