Immunology and Infectious Disease Commons^™

Efficacy Of The Pentavalent Rotavirus Vaccine, Rotateq (Rv5), Between Doses Of A 3-Dose Series And With Less Than 3 Doses (Incomplete Regimen), Penelope D. Dennehy, Timo Vesikari, David O. Matson, Robbin F. Itzler, Michael J. Dallas, Michelle G. Goveia, Mark J. Dinubile, Penny M. Heaton, Max Ciarlet

Community & Environmental Health Faculty Publications

Post-hoc analyses of the Rotavirus Efficacy and Safety Trial (RES T) were conducted to determine whether the pentavalent rotavirus vaccine (RV5) confers early protection against rotavirus gastroenteritis (RVGE) before completion of the 3-dose regimen. To evaluate the efficacy of RV5 between doses in reducing the rates of RVGE-related hospitalizations and emergency department (ED) visits in infants who ultimately received all 3 doses of RV5/placebo, events occurring from 2 weeks after the first and second doses to receipt of the subsequent dose (Analysis A) and events occurring from 2 weeks after the first and second doses to 2 weeks after the …

Mathematical Model To Assess The Relative Effectiveness Of Rift Valley Fever Countermeasures, Holly Gaff, Colleen Burgess, Jacqueline Jackson, Tianchan Niu, Yiannis Papelis, David Hartley

Biological Sciences Faculty Publications

Mathematical modeling of infectious diseases is increasingly used to explicate the mechanics of disease propagation, impact of controls, and sensitivity of countermeasures. The authors demonstrate use of a Rift Valley Fever (RVF) model to study efficacy of countermeasures to disease transmission parameters. RVF is a viral infectious disease that propagates through infected mosquitoes and primarily affects animals but also humans. Vaccines exist to protect against the disease but there is lack of data comparing efficacy of vaccination with alternative countermeasures such as managing mosquito population or destroying infected livestock. This paper presents a compartmentalized multispecies deterministic ordinary differential equation model …

The Innate Anti-Hiv-1 Activity Of Human Seminal Plasma, Julie A. Martellini-Moore

Electronic Theses and Dissertations

Human immunodeficiency virus (HIV) has become a global pandemic over the past few decades, with new infections and related deaths in the millions each year. There is no cure in sight for HIV-1 infection, and there has been little progress in developing an efficacious vaccine. Heterosexual transmission of HIV-1 remains the principal mode of transmission throughout the world and thus measures, such as topical vaginal microbicides, to prevent infection of the female reproductive tract are actively being explored. Recent trials of topical vaginal microbicides have shown that their interaction with the mucosal surfaces of the female reproductive tract as well …

Preventing Mother-To-Child Transmission Of Human Immunodeficiency Virus-1 (Hiv-1): Effects Of Intrapartum And Neonatal Single-Dose Nevirapine Prophylaxis And Subsequent Hiv-1 Drug Resistance At Antiretroviral Treatment Initiation, Amanda L. Harmon

CMC Senior Theses

The prevention of mother-to-child transmission is one of the most powerful tools in human immunodeficiency virus type 1 (HIV-1) prevention and has huge potential to improve both maternal and child health. In the absence of any preventative measures, infants born to and breastfed by their HIV-positive mothers have roughly a one-in-three chance of acquiring the infection themselves. HIV can be passed on from mother-to-child during pregnancy, during labor and delivery, and even after during breastfeeding.

Intrapartum and neonatal single-dose nevirapine (sd-NVP) is the foundation of preventing mother-to-child transmission in lower resource settings where it has been used alone or as …

The Role Of Hiv-1 Proteins In Alzheimer's Disease Pathology, Brian Nelson Giunta

USF Tampa Graduate Theses and Dissertations

Prevalence of HIV-associated cognitive impairment is rising, the worst form of which is HIV-associated dementia (HAD). The disease is fuiled by a chronic innate type pro-inflammatory response in the brain which is highly dependent upon the activation of microglia. We first created an in vitro model of HAD composed of cultured microglial cells synergistically activated by the addition of IFN-gamma and the HIV-1 coat glycoprotein, gp120. This activation, as measured by TNF-alpha and NO release, is synergistically attenuated through the alpha7nAChR and p44/42 MAPK system by pretreatment with nicotine, and the cholinesterase inhibitor, galantamine. As these medications have been FDA …

Generation And Application Of Antigen-Specific Induced Regulatory T Cells In Allogeneic Bone Marrow Transplantation, Kenrick Semple

USF Tampa Graduate Theses and Dissertations

CD28 co-stimulation is required for the generation of naturally occurring regulatory T cells (nTregs) in the thymus through Lck-signaling. However, high level of CD28 suppresses the generation of induced Tregs (iTregs) from naïve CD4 T cells, although underlying mechanism(s) has not been defined. Here we investigated the role of CD28-mediated signaling pathways in the suppression of Treg generation. We used a series of transgenic (Tg) mice on CD28-deficient background that bears WT CD28 or mutated CD28 in its cytosolic tail incapable of binding to Lck, PI3K or Itk. Regardless of exogenous IL-2, strong CD28 costimulation suppressed iTreg generation through Lck …

Novel Roles For The Transcriptional Repressor Prdm1 In Human Natural Killer Cells And Identification Of An Inhibitor Of Its Interacting Methyltransferase G9a, Matthew Adams Smith

USF Tampa Graduate Theses and Dissertations

The studies presented within this dissertation provide the first description of PRDM1 (also known as Blimp-1 or PRDI-BF1) function in natural killer cells. NK cells are major effectors of the innate immune response via antigen-independent cytotoxicity and link to the adaptive immune response through cytokine release. Molecular mechanisms mediating NK activation are relatively well-studied; however, much less is known about the mechanisms that restrain activation.

In the first study, the transcriptional repressor PRDM1 is shown to be a critical negative regulator of NK function. Microarray analysis was used to characterize transcriptional changes associated with cytokine-mediated activation. PRDM1 is expressed at …

Development Of A Non-Invasive Electrode For Intradermal Electrically Mediated Dna Vaccination, Amy Lynn Donate

USF Tampa Graduate Theses and Dissertations

Current progress in the development of vaccines has decreased the incidence of fatal and non-fatal infections and increased longevity. However, new technologies need to be developed to combat an emerging generation of infectious diseases. DNA vaccination has been demonstrated to have great potential for use against a wide variety of diseases. Alone, this vaccine technology does not generate a significant immune response for vaccination, but combined with delivery by electroporation (EP), can enhance plasmid expression and immunity against the expressed antigen. Most EP systems, while effective, can be invasive and painful making them less desirable for use in vaccination. Our …

Ctla-4 Transcriptional Activation: Regulation Of Induced Expression, Heather Gibson

Wayne State University Dissertations

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a T cell surface protein that is homologous to CD28 and binds to the B7 family of ligands. Unlike CD28, CTLA-4 interaction transmits a negative signal in T cells, leading to suppression of proliferation. CTLA-4 is constitutively expressed on regulatory T cells (Tregs) but is also inducible in effector T cells. The mechanisms driving transcriptional regulation of CTLA-4 are poorly understood. Our previous work identified a bona fide NFAT1 binding site in the proximal promoter for effector T cells. In addition, we found histone acetylation occurred after stimulation.

As a result of its role …

Identification And Characterization Of Equine Rotaviruses In Southern Ireland, Crystal Cronin

Theses

Group A Rotaviruses(GARVs) are enteric pathogens which induce acute gastroenteritis in infants, neonates and the young of many animal species. During a 4 year study (2005-2009), 64 fecal samples from symptomatic foals, from several counties, in the south of Ireland, were molecularly characterized to determine the VP& (G type), VP4 (P type), and NSP4 antigenic specificities. Globally, G3 [P12] and G14[P12] are recognized as the predominant equine GARV strains. Twenty-two samples (34.38%) were found to contain G3 viruses, while 21 samples (32.81%) contained G14 viruses. In this study, there was a distinct increase in the incidence of mixed infections circulating …

Hsv-1 Infection In Keratinocyte Cell Lines Treated With Mitotic Inhibitors, Asma A. Abbas

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The hypothesis for this research was: Herpes simplex virus type 1 (HSV-1) infection of murine keratinocyte cell lines (HEL-30 and PAM-212) treated with mitotic inhibitors leads to silencing of virus replication. At 0.1 (Multiplicity of infection) MOI, PAM-212 keratinocytes showed some cell lysis and viral plaques were seen in HEL-30 keratinocyte cultures. PAM-212 keratinocytes, infected at 0.01 MOI, were more susceptible to the lytic effect of HSV-1 than were HEL-30 cells. In this study, 5-fluoro-2'-deoxyuridine (FUDR) treatment of both keratinocyte cell lines permitted an increase survival of HSV-1- infected keratinocytes especially for PAM-212 cell line which was further examined for …

Distribution Of Cellular Interferon Beta (Ifn-Β) In Murine Fibroblast Cell Lines Upon Infection Of Hsv-1, Rachael E. Curtis

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The hypothesis for this study was: IFN-β expression differs between murine fibroblasts (A2R1 and L929) of different mouse strains upon infection of HSV-1. Fluorescent microscopy was used to examine localization of IFN-β in the different murine fibroblast and keratinocyte cell lines after 6 hours of infection with herpes simplex virus type-1 (HSV-1). Because keratinocytes cell lines HEL-30 and PAM-212 grew in clusters, staining patterns in individual cells could not be determined. A notable difference in localization of IFN-β immune staining was seen between the two cell lines when infected with HSV-1. The A2R1 cell line showed perinuclear (PN) localization, while …

Targeted Knockdown Of Amp-Activated Protein Kinase Alpha 1 And Alpha 2 Catalytic Subunits, Larissa J. Tangeman

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AMP-activated protein kinase (AMPK) regulates cellular metabolism and promotes ATP production when energy is depleted. Evidence suggests that AMPK may be involved in oxygen sensing by carotid body cells, which are responsible for regulating the breathing rate to maintain proper blood oxygen levels. There are two isoforms of the catalytic alpha subunit, AMPKalpha1 and AMPKalpha2, which could be involved in oxygen sensing. Here, the production of a short hairpin RNA (shRNA) targeting both catalytic isoforms of AMPK in human, mouse, and rat is described. The shRNA causes significant knockdown of both isoforms of AMPK alpha in mouse and human cells …

Strategies For Long-Term Renal Allograft Survival In Iga Nephropathy Patients, Erin E. Lintz

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IgA nephropathy is one of the most common kidney diseases worldwide. Most IgA nephropathy patients will undergo a kidney transplant as a treatment. Treatment currently includes the use of immunosuppressants which are necessary to prevent graft rejection but present harmful side-effects when taken long-term. This review focuses on strategies which have the ability to promote tolerance of both donor and recipient cells within a transplant recipient. Such strategies allow development of mixed chimerism and thereby alleviate the need for long-term immunosuppressant usage in allograft recipients. These strategies could be applied to IgA nephropathy patients to allow kidney allograft acceptance without …

Amino Acid Substitutions Created In Reverse Transcriptase And Their Influence On Hiv-1 Mutation Frequencies, Amani Saud Alhejely

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As research has shown, a high mutation rate occurs during the reverse transcription RT process because HIV reverse transcriptase fails to correct erroneously incorporated nucleotides during the reverse transcription process. Based on various research articles, a series of amino acid substitutions created in RT were collected to find out their influence on virus mutation frequencies. Two tables were used; one for amino acid substitutions created in RT that increased the HIV-1 mutation rate and another for amino acid substitutions created in RT that decreased the HIV-1 mutation rate. The tables show which amino acid substitutions created in RT decreased or …

Developing A Quantitative Pcr Assay For Detecting Viral Vector Shedding From Animals, Swathee Chinnasamy

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Replication deficient viruses have been used widely for replacing, repairing, and deleting target genes. These recombinant viruses are tested on research animals or patients in clinical trials. Although viral vectors distribute in the body, they are also disseminated into the environment through secretion and excretion processes. By studying the extent of shedding, a proper risk assessment can be performed and appropriate biocontainment can be achieved. Adenoviral and lentiviral vectors were produced from commercially available kits. The transgene present in both vector systems was the lacZ reporter gene encoding for β-galactosidase. Primers and probes were designed for the encapsidation region of …

Some Laelapine Mites (Acari: Laelapidae) Ectoparasitic On Small Mammals In The Galapagos Islands, Including A New Species Of Gigantolaelaps From Aegialomys Galapagoensis, Donald D. Gettinger, Fernanda Martins-Hatano, Scott Lyell Gardner

Scott L. Gardner Publications

A collection of laelapine mites from small mammals in the Galapagos Islands are identified and their host distributions reviewed. Two species of native rodents, Aegialomys galapagoensis and Nesoryzomys narboroughii, were infested only with species typical of Neotropical oryzomyine rodents; Rattus rattus was infested with Laelaps nuttalli, a host-specific ectoparasite to Old World Rattus. A synopsis of Gigantolaelaps Fonseca is provided and we describe a new laelapine mite, Gigantolaelaps aegialomys n. sp., from the pelage of the rodent A. galapagoensis on Santa Fe Island. The new species has strong morphological affinities with a subgroup of Gigantolaelaps associated …

Carbenoxolone Blocks The Light-Evoked Rise In Intracellular Calcium In Isolated Melanopsin Ganglion Cell Photoreceptors, Jayne R. Bramley, Erin M. Wiles, Patricia J. Sollars, Gary E. Pickard

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Retinal ganglion cells expressing the photopigment melanopsin are intrinsically photosensitive (ipRGCs). These ganglion cell photoreceptors send axons to several central targets involved in a variety of functions. Within the retina ipRGCs provide excitatory drive to dopaminergic amacrine cells via glutamatergic signals and ipRGCs are coupled to widefield GABAergic amacrine cells via gap junctions. However, the extent to which ipRGCs are coupled to other retinal neurons in the ganglion cell layer via gap junctions is unclear. Carbenoxolone, a widely employed gap junction inhibitor, greatly reduces the number of retinal neurons exhibiting non-rod, non-cone mediated light-evoked Ca²⁺ signals suggesting extensive …

Intrinsically Photosensitive Retinal Ganglion Cells, Gary E. Pickard, Patricia J. Sollars

School of Veterinary and Biomedical Sciences: Faculty Publications

Intrinsically photosensitive retinal ganglion cells (ipRGCs) respond to light in the absence of all rod and cone photoreceptor input. The existence of these ganglion cell photoreceptors, although predicted from observations scattered over many decades, was not established until it was shown that a novel photopigment, melanopsin, was expressed in retinal ganglion cells of rodents and primates. Phototransduction in mammalian ipRGCs more closely resembles that of invertebrate than vertebrate photoreceptors and appears to be mediated by transient receptor potential channels. In the retina, ipRGCs provide excitatory drive to dopaminergic amacrine cells and ipRGCs are coupled to GABAergic amacrine cells via gap …

Long-Term Clinicopathological Characteristics Of Alpacas Naturally Infected With Bovine Viral Diarrhea Virus Type Ib, D. Bedenice, Edward J. Dubovi, Clayton Kelling, Jamie N Henningson, Christina L. Topliff, N. Parry

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Substantial bovine viral diarrhea virus (BVDV)-related production losses in North American alpaca herds have been associated with BVDV type Ib infection.

Objectives: To classify and differentiate the long-term clinicopathological characteristics of BVDV type Ib infection of al- paca crias, after natural virus exposure. We hypothesized that persistently infected (PI) alpacas specifically demonstrate growth retardation, clinicopathological evidence of opportunistic infections, and early mortality.

Animals: Thirty-five crias naturally exposed to BVDV (18 acute, 3 chronic, 14 PIs), and 19 healthy cohort controls of 5 northeastern alpaca farms were prospectively evaluated over 2 years (September 2005–September 2008).

Methods: Observational cohort-control study.

Results: …