- Browse by Subject
Browsing by Subject "HIV vaccine"
Now showing 1 - 4 of 4
Results Per Page
Sort Options
Item Barriers, Facilitators, and Suggestive HIV Interventions for Women: Preliminary Data from a Secondary Analysis(Office of the Vice Chancellor for Research, 2013-04-05) Schmitt, Herman C.; Burrage, JoeThe Centers for Disease Control and Prevention report that women account for almost ten thousand of those newly diagnosed with HIV annually. Within this group, Latina, non-Latina white and non-Latina black women are particularly affected. The purpose of this secondary analysis was to analyze existing de-identified data for barriers and facilitators for HIV testing and willingness to participate in a vaccine if available. The data were 30 de-identified transcripts of one hour interviews obtained from three groups of women (10 Latinas, 10 non-Latina white, and 10 non- Latina black) during the initial phase of a parent study, “HIV Testing and Women’s Attitudes on HIV Vaccine Trials”: G. Zimet, PI. A semi-structured interview guide had been used to guide the interviews. This sub analysis was conducted with removal of ethnic classification to reduce bias during qualitative review. Three predominant categories of fear, time, and cost emerged from all interviews regardless of ethnicity. Less prominent categories of gender, education, trust, motherhood, discrimination, loss of integrity, invincibility, safety, age, testing accuracy, confidentiality, indifference, pride, lifestyle, divine justice, and stress varied among the three groups. These categories will provide the basis for further analysis to determine subthemes and themes, and if there are themes unique to any of the three groups.Item Elucidating the role of BCL6 in helper T cell activation, proliferation, and differentiation(2014) Hollister, Kristin N.; Dent, Alexander L.; Brutkiewicz, Randy R.; Harrington, Maureen A.; Kaplan, Mark H.The transcriptional repressor BCL6 has been shown to be essential for the differentiation of germinal center (GC) B cells and follicular T helper (TFH) cells. The interaction of TFH and GC B cells is necessary for the development of high affinity antibodies specific for an invading pathogen. Germline BCL6-deficient mouse models limit our ability to study BCL6 function in T cells due to the strong inflammatory responses seen in these mice. To overcome this, our lab has developed a new BCL6 conditional knockout (cKO) mouse using the cre/lox system, wherein the zinc finger region of the BCL6 gene is flanked by loxP sites. Mating to a CD4-Cre mouse allowed us to study the effects of BCL6 loss specifically in T cells, without the confounding effects seen in germline knockout models. Using this cKO model, we have reaffirmed the necessity of BCL6 for TFH differentiation, including its role in sustained CXCR5 surface expression, a signature marker for TFH cells. This model also allowed us to recognize the role of BCL6 in promoting the expression of PD-1, another key surface marker for TFH cells. Without BCL6, CD4+ T cells cannot express PD-1 at the high levels seen on TFH cells. Our discovery of DNMT3b as a target for BCL6 suggests BCL6-deficient T cells have increased DNA methyltransferase activity at the PD-1 promoter. This data establishes a novel pathway for explaining how BCL6, a transcriptional repressor, can activate genes. Experiments with the BCL6 cKO model have also established a role for BCL6 in naïve CD4+ T cell activation. Furthermore, we did not observe increased differentiation of other helper T cell subsets, in contrast to what has been reported elsewhere with germline BCL6-deficient models. Unexpectedly, we found decreased T helper type 2 (Th2) cells, whereas mouse models with a germline mutation of BCL6 have increased Th2 cells. These results indicate that BCL6 activity in non-T cells is critical for controlling T cell differentiation. Finally, using an HIV-1 gp120 immunization model, we have, for the first time, shown BCL6-dependent GCs to be limiting for antibody development and affinity maturation in a prime-boost vaccine scheme.Item Human Antibody-Dependent Cellular Cytotoxicity-Mediating Antibodies Do Not Recruit Non-Human Primate CD20+ NK Cells(2018-04) Asdell, Stephanie M.; Edwards, R. Whitney; Jha, Shalini; Ferrari, GuidoThe antibody-dependent cell-mediated cytotoxicity (ADCC) response represents one of mechanisms through which the immune system destroys tumor or infected cells. During the ADCC response to HIV-1, natural killer (NK) cells are recruited by natural infection- or vaccine-induced antibodies (Abs) bound to the HIV-1 envelope glycoproteins expressed on infected CD4+ T cells via Fc-gamma Receptor IIIA (Fc-R IIIA). The NK cells’ Ab-mediated recognition of the infected cells leads to the release of granzymes and perforin by degranulation, triggering apoptotic signal pathways in the infected cells and ultimately leading to their elimination. We have optimized an assay to investigate the degranulation of non-human primate (NHP) NK cells from five different NHP donors by measuring levels of CD107a, a marker present on the inner membranes of NK lysosomes. Using one NHP and two human monoclonal antibodies (mAbs), we compared degranulation of NK in NHP splenocytes, NHP peripheral blood mononuclear cells (PBMC), and human PBMC. We observed that both NHP and human mAbs recruited NHP and human NK effector cells. Of note, we examined the activity of CD20+ and CD20- NK cells, with the former being NK cells from a unique subset of NHP NK splenocytes. Our analysis suggests that CD20+ cells likely do not play a role in the NHP ADCC response. In conclusion, we can identify the cellular populations responsible for the Ab-mediated killing of HIV-1 infected cells, and we will be able to further analyze their full functional profile at the level of messenger RNA expression, i.e. their transcriptomic profile.Item The role of follicular helper T cells and the germinal center in HIV-1 gp120 DNA prime and gp120 protein boost vaccination(Taylor & Francis, 2014-07) Hollister, Kristin; Chen, Yuxin; Wang, Shixia; Wu, Hao; Mondal, Arpita; Clegg, Ninah; Lu, Shan; Dent, Alexander; Department of Microbiology and Immunology, IU School of MedicineThe importance of follicular T helper (TFH) cells and the germinal center (GC) reaction in the humoral immune response has become clear in recent years, however the role of TFH cells and the GC in an HIV vaccine strategy remains unclear. In this study, we primed mice with gp120-encoding DNA and boosted with gp120 protein, a regimen previously shown to induce high titers of high affinity and cross-reactive anti-gp120 Abs. Priming with gp120 DNA caused increased TFH cell differentiation, GC B cells, and antigen-specific antibody titers, compared with priming with gp120 protein. Priming with DNA also caused more activated CD4(+) T cells to become TFH cells and more GC B cells to become memory cells. Deletion of BCL6 midway through the vaccine regimen resulted in loss of TFH cells and GCs, and, unexpectedly, increased anti-gp120 IgG titers and avidity. Our data suggests vaccination with gp120-encoding DNA elicits a stronger and more rapid TFH and GC response than gp120 protein. Furthermore, we demonstrate that the GC reaction may actually limit antigen-specific IgG secretion in the context of repeated immunizations.