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Novel Strategies To Develop Better Brucellosis Vaccines Using Brucella Abortus Rb51 And B. Neotomae, Neha Dabral

Open Access Dissertations

The genus Brucella consists of Gram-negative, facultative intracellular coccobacilli that can cause chronic infections in several mammals. Brucella spp. can exhibit a smooth or rough phenotype; smooth Brucella spp. contain a surface-exposed O-polysaccharide in their cell wall structure while the rough Brucella spp. are devoid of the O-polysaccharide. Acquired immunity against Brucella infection is primarily cell-mediated and involves both CD4+ T cells and CD8+ T cell responses. However, antibodies to the O-polysaccharide also play a role in enhancing the protection against infections by virulent Brucella species in some hosts. B. abortus strain RB51 is a stable rough attenuated mutant which …

Modulation Of Vaccine-Induced Responses By Anthelmintic Treatment In Ponies, Emily Rubinson

Theses and Dissertations--Medical Sciences

Vaccines and anthelmintics induce an inflammatory response in equids. Since they are commonly given concurrently, it is practical to study any interaction between them. This study evaluated whether IVM and PYR would modulate the acute phase inflammatory response, the systemic gene expression of pro-inflammatory cytokines, and vaccine-specific titers induced by WNV, EHV, and KLH vaccines. Naturally-infected, yearling ponies were sorted by gender, then fecal epgs. They were randomly assigned to three treatment groups: IVM, PYR, and control. All ponies received vaccinations intramuscularly on days 0 and 29. Whole blood, serum, and plasma samples were collected 1, 3, and 14 days …

Vaccines Within Vaccines: The Use Of Adenovirus Types 4 And 7 As Influenza Vaccine Vectors, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

adenovirus Types 4 and 7 (ad4 and ad7) are associated with acute respiratory distress (aRD). In order to prevent wide- spread ad-associated aRD (ad-aRD) the United states military immunizes new recruits using a safe and effective lyophi- lized wildtype ad4 and ad7 delivered orally in an enteric-coated capsule. We cloned ad4 and ad7 and modified them to express either a GFP-Luciferase (GFPLuc) fusion gene or a centralized influenza H1 hemagglutinin (Ha1-con). BaLB/c mice were injected with GFPLuc expressing viruses intramuscularly (i.m.) and intranasally (i.n.). ad4 induced significantly higher luciferase expression levels as compared with ad7 by both routes. ad7 transduction …

Characterization Of Nipah Virus Pathogenicity In Vitro And In Vivo And Protection From Disease Using A Single Dose Recombinant Vaccine, Blair Lynn Debuysscher

Graduate Student Theses, Dissertations, & Professional Papers

Nipah virus is a zoonotic pathogen that infects a wide species range including humans. It was first discovered in Malaysia in 1998 during a large outbreak, but since has spread to Bangladesh and India causing almost yearly outbreaks in the region since 2001. The distinct geographic locations have led to two genetically varied strains. Infection of humans by Nipah virus leads to respiratory distress and acute encephalitis. Pathology caused by the virus is characterized by vasculitis, necrosis, and edema of small vessels of the lung and brain primarily. This work investigates differences of pathology and clinical signs in the hamster …

Immunoproteomic Analysis Of Proteins Expressed By Two Related Pathogens, Burkholderia Multivorans And Burkholderia Cenocepacia, During Human Infection., Minu Shinoy, Ruth Dennehy, Lorraine Coleman, Stephen Carberru, Kirsten Schaffer, Máire Callaghan, Sean Doyle, Siobhan Mcclean

Articles

Burkholderia cepacia complex (Bcc) is an opportunistic bacterial pathogen that causes chronic infections in people with cystic fibrosis (CF). It is a highly antibiotic resistant organism and Bcc infections are rarely cleared from patients, once they are colonized. The two most clinically relevant species within Bcc are Burkholderia cenocepacia and Burkholderia multivorans. The virulence of these pathogens has not been fully elucidated and the virulence proteins expressed during human infection have not been identified to date. Furthermore, given its antibiotic resistance, prevention of infection with a prophylactic vaccine may represent a better alternative than eradication of an existing infection. We …

A Review Of Vaccine Approaches For West Nile Virus, Arun V. Iyer, Konstantin G. Kousoulas

Faculty Publications

The West Nile virus (WNC) first appeared in North America in 1999. The North American lineages of WNV were characterized by the presence of neuroinvasive and neurovirulent strains causing disease and death in humans, birds and horses. The 2012 WNV season in the United States saw a massive spike in the number of neuroinvasive cases and deaths similar to what was seen in the 2002-2003 season, according to the West Nile virus disease cases and deaths reported to the CDC by year and clinical presentation, 1999-2012, by ArboNET (Arboviral Diseases Branch, Centers for Disease Control and Prevention). In addition, the …

Envelope Determinants Of Equine Lentiviral Vaccine Protection, Jodi K. Craigo, Corin Ezzelarab, Sheila J. Cook, Chong Liu, David W. Horohov, Charles J. Issel, Ronald C. Montelaro

Veterinary Science Faculty Publications

Lentiviral envelope (Env) antigenic variation and associated immune evasion present major obstacles to vaccine development. The concept that Env is a critical determinant for vaccine efficacy is well accepted, however defined correlates of protection associated with Env variation have yet to be determined. We reported an attenuated equine infectious anemia virus (EIAV) vaccine study that directly examined the effect of lentiviral Env sequence variation on vaccine efficacy. The study identified a significant, inverse, linear correlation between vaccine efficacy and increasing divergence of the challenge virus Env gp90 protein compared to the vaccine virus gp90. The report demonstrated approximately 100% protection …

Bridging The Gap: Using The Theory Of Planned Behavior To Predict Hpv Vaccination Intentions In Men, Daniel Snipes

Theses and Dissertations

Genital human papillomavirus (HPV) is the most common sexually transmitted infection (STI) in the US, with an estimated incidence rate of 6.2 million new cases each year. Men have higher instances of certain HPV related outcomes (e.g., head/neck cancers) when compared to women, so male vaccination with the HPV vaccine is also paramount to preventing cancer. The present study examined the theory of planned behavior (TPB) as a model for predicting HPV vaccination intentions among men. Results suggest the TPB was a well-fitting model to the data, but not all aspects of the TPB model were predictive of HPV vaccination …

Cpg And Interleukin-15 Synergize To Enhance Ifn-Gamma Production By Activated Cd8(+) T Cells, Dustin Cobb, Sigi Guo, Ronald B. Smeltz

Bioelectrics Publications

Interleukin-15 (IL-15) regulates the development and maintenance of memory CD8(+) T cells. Paradoxically, we previously reported that IL-15 could enhance CD8(+) T-cell responses to IL-12, a proinflammatory cytokine required for optimal priming of effector CD8(+) T cells. To expand the physiological relevance of these findings, we tested IL-15 for its ability to enhance T-cell responses to bacterial CpG. Expectedly, CpG enhanced the production of IFN-gamma by CD8(+) T cells polyclonally activated with anti-CD3. However, addition of IL-15 to CpG-stimulated cultures led to a striking increase in IFN-gamma production. The effect of CpG and IL-15 was also evident with CD8(+) T …

Neutralizing Antibodies Against The Ricin Toxin Binding Subunit (Rtb), Anastasiya Yermakova

Legacy Theses & Dissertations (2009 - 2024)

Ricin is a toxin that is naturally produced by the seeds of the castor bean plant Ricinus communis, and is part of a family of A-B toxins that includes Shiga, cholera, and anthrax toxins. The toxin consists of two subunits, RTA and RTB, which are linked by a disulfide bond. RTA is an RNA N-glycosidase that selectively targets and inactivates 28S ribosomal RNA, thereby arresting protein synthesis and leading to cell death. RTB is a galactose/ N-acetylgalactosamine-specific lectin that mediates attachment, entry, and intracellular trafficking of ricin in host cells. Currently, there is no approved vaccine or therapeutics available against …

Development And Evaluation Of A Replicon Particle Vaccine Expressing The E2 Glycoprotein Of Bovine Viral Diarrhea Virus (Bvdv) In Cattle, John Dustin Loy, Jill Gander, Mark Mogler, Ryan Vander Veen, Julia Ridpath, Delbert Hank Harris, Kurt Kamrud

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Bovine viral diarrhea virus is one of the most significant and costly viral pathogens of cattle worldwide. Alphavirus-derived replicon particles have been shown to be safe and highly effective vaccine vectors against a variety of human and veterinary pathogens. Replicon particles are non-propagating, DIVA compatible, and can induce both humoral and cell mediated immune responses. This is the first experiment to demonstrate that Alphavirus-based replicon particles can be utilized in a standard prime/boost vaccination strategy in calves against a commercially significant bovine pathogen.

Findings: Replicon particles that express bovine viral diarrhea virus sub-genotype 1b E2 glycoprotein were …

Mucin Associated Surface Protein Synthetic Peptide As A Novel Vaccine Candidate Against Chagas Disease, Carylinda Serna

Open Access Theses & Dissertations

Trypanosoma cruzi is an intracellular protozoan parasite and the etiological agent for Chagas disease. Chagas is endemic in Latin America affecting 18-20 million people. However, currently worldwide increasing numbers of the disease are being seen due to migration and globalization. This neglected disease causes significant morbidity, mortality, and an economic burden. There are no known vaccines and the only currently available drug is Benznidazole, but its effects are controversial. Nonetheless, a therapeutic or prophylactic vaccine is of urgent need to alleviate this disease. In this study we present an experimental approach using a synthetic peptide-based vaccine against T. cruzi. The …

Defining A Role For Inducible Heat Shock Protein 70 (Hsp70i) In Mediating Autoimmune Vitiligo, Jeffrey Alan Mosenson

Dissertations

Vitiligo is an autoimmune disease characterized by destruction of melanocytes, leaving 0.5% of the population with progressive depigmentation. Current treatments offer limited efficacy. Observations that heat shock proteins (HSPs) can serve as adjuvants in antitumor vaccines first suggested to us a link between HSPs and stress-induced vitiligo. Such proteins are marvelously well conserved throughout evolution, which has placed them in the spotlight for helping to understand the intriguing relationship between infection and immunity. Intracellularly, inducible heat shock protein 70 (HSP70i) is upregulated by stress and helps protect cells from undergoing apoptosis. In times of stress, melanocytes will secrete antigen bound …

Antibodies To Inhibit Clostridium Difficile Adhesion To Human Gut Epithelial Cell Line, Wonbeom Paik

Master's Theses

Clostridium difficile infection (CDI) is a major hospital-acquired diarrhea that can cause life-threatening complications such as pseudomembranous colitis. CDI is caused by colonization of host with C. difficile, a Gram positive, anaerobic bacterium known to produce toxins that cause disease. Normally, the gut microbiota protects the host from CDI, but disruption of the microbial composition through antibiotic treatment can leave one vulnerable for CDI. To date, no vaccines for preventing CDI are available.

In this study, the potential of antibodies directed against specific surface molecules of C. difficile to block bacterial adherence to host gut epithelial cells was studied, in …

Induction Of Stronger And Long Lasting Vaccine Immunity To Tuberculosis, Pearl Bakhru

Dissertations and Theses (Open Access)

Tuberculosis is a major cause of death due to an infection in mankind. BCG vaccine protects against childhood tuberculosis although, it fails to protect against adult tuberculosis. BCG vaccine localizes to immature phagosomes of macrophages, and avoids lysosomal fusion, which decreases peptide antigen production. Peptides are essential for macrophage-mediated priming of CD4 and CD8 T cells respectively through MHC-II and MHC-I pathways. Furthermore, BCG reduces the expression of MHC-II in macrophages of mice after infection, through Toll-like receptor-1/2 (TLR-1/2) mediated signaling. In my first aim, I hypothesized that BCG-induced reduction of MHC-II levels in macrophages can decrease CD4 T cell …

Immunoproteomics: The Key To Discovery Of New Vaccine Antigens Against Bacterial Respiratory Infections, Ruth Dennehy, Siobhan Mcclean

Articles

The increase in antibiotic resistance and the shortage of new antimicrobials to prevent difficult bacterial infections underlines the importance of prophylactic therapies to prevent infection by bacterial pathogens. Vaccination has reduced the incidence of many serious diseases, including respiratory bacterial infections. However, there are many pathogens for which no vaccine is available and some vaccines are not effective among all age groups or among immunocompromised individuals. Immunoproteomics is a powerful technique which has been used to identify potential vaccine candidates to protect against pathogenic bacteria. The combination of proteomics with the detection of immunoreactive antigens using serum highlights immunogenic proteins …

The Effect Of Mixing Events On The Dynamics Of Ph1n1 Outbreaks At Small Residential Colleges, Karen Palin, Meredith Greer

All Faculty Scholarship

Objective: The authors examine the dynamics and the impact of all-campus events on pH1N1 spread at Bates College in fall 2009, with comparisons to 3 other campuses. Participants: Students (N = 285) presented or called in to the Bates Health Center with symptoms consistent with influenza-like illness. Methods: Health Center staff at Bates collected data on the outbreak; data from other colleges are from Web sites and journal articles. Data were analyzed using a mathematical model for influenza. Results: Bates held 2 vaccine clinics mid-outbreak. The data are consistent with the hypothesis that the vaccine clinics may have altered …

A Structural Perspective Of Antibody Neutralization Of Dengue Virus, Stephen Kyle Austin

All Theses and Dissertations (ETDs)

The four dengue viruses: DENV) are mosquito-borne flaviviruses and are considered the world's most significant arboviruses in terms of worldwide disease burden. Symptoms of dengue disease are classified into dengue fever, a mild, febrile illness, and the potentially fatal severe dengue, which can include hemorrhaging and shock. Antibody protection against DENV correlates with the production of neutralizing antibodies against the envelope: E) glycoprotein.

To understand the role of antibodies in DENV infection, we sought to dissect the relationship between epitope and function. Virologic studies had identified that the most potently neutralizing antibodies are against domain III: DIII) of the E …

Dynamic Pricing Strategy To Optimally Allocate Vaccines, Mauricio Pommier Gasser

Theses

In the United States, the Advisory Committee on Immunization Practices (ACIP) makes recommendations as to which cohorts (identified groups of individuals) ought to have higher priority access to vaccines when their supply is insufficient to immunize all susceptible individuals in the country. Typically, cohorts are determined based on susceptibility to contracting seasonal influenza and on the resulting consequences of infection for different age groups. For seasonal influenza, high-risk cohorts commonly include children, teenagers, pregnant women and people with different chronic diseases. This study proposes the application of revenue management theory to better allocate seasonal influenza vaccines among different risk-based population …

Effects Of Respiratory Vaccination Timing And Hormonal Growth Implant On Health, Performance, And Immunity Of Newly Received Stocker Calves, Kimberly Denise Poe

Graduate Theses and Dissertations

Stress alters the immune system and vaccination during this time may reduce vaccine response; whereas, growth implants may shift metabolism to enhance tissue deposition in exchange for energy required for immune response during bovine respiratory disease (BRD) challenge. This study was conducted to determine the effects of pentavalent respiratory vaccination timing with or without a hormonal growth implant on arrival (d 0) on health, performance, complete blood count, and vaccine response in high&ndashrisk, newly received stocker calves during a 42&ndashd receiving period. Crossbred bull and steer calves (n = 385) were weighed (initial BW = 202 ± 4.1 kg), stratified …

A Social Controversy: Autism Spectrum Disorder's Correlation To The Measles-Mumps-Rubella Vaccination, Lindsay A. Frye

Senior Honors Theses

A 1998 research study lead by Dr. Andrew Wakefield linked the measles-mumps-rubella (MMR) vaccination as a probable cause to autism spectrum disorder. This publication has started a significant debate among healthcare professionals and instigated an anti-vaccination movement within the general population. This vaccination controversy was started by parents who readily accepted Wakefield’s findings as truth and frequently would choose to withdrawal the administration of vaccinations from their children’s care plans. There has also been disapproval by healthcare professionals over Wakefield’s study since numerous research teams have been unable to replicate his findings. This disagreement surrounding the MMR vaccination is likely …

Enhancing The Immune Response Through Ikkbeta-Induced Activation Of Nf-Kappab, Emily Hopewell

USF Tampa Graduate Theses and Dissertations

Nuclear factor-κB (NF-κB) is one of the main regulators of inflammatory and immune responses. It is a family of transcription factors composed of five members: RelA, RelB, cRel, NF-κB1 (p105/p50), and NF-κB2 (p100/p52). Homo- and hetero-dimers of family members are inhibited by inhibitor of &klappaB (IκB) family members and activated by IκB kinase (IKK) family members. The IKK family is comprised of IKKα, IKKΒ, and IKKγ. The focus of my dissertation delves into the role of NF-κB activation by IKKΒ in both an immunotherapy setting and its role in T cell mediated anti-tumor immune responses.

A central focus of immunotherapy …

Schools As Potential Vaccination Venue For Vaccines Outside Regular Epi Schedule: Results From A School Census In Pakistan., Sajid Bashir Soofi, Inam-Ul Haq, M. Imran Khan, Muhammad Bilal Siddiqui, Mushtaq Mirani, Rehman Tahir, Imtiaz Hussain, Mahesh K Puri, Zamir Hussain Suhag, Asif R Khowaja, Abdul Razzaq Lasi, John D Clemens, Michael Favorov, R. Leon Ochiai, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

Background: Vaccines are the most effective public health intervention. Expanded Program on Immunization (EPI) provides routine vaccination in developing countries. However, vaccines that cannot be given in EPI schedule such as typhoid fever vaccine need alternative venues. In areas where school enrolment is high, schools provide a cost effective opportunity for vaccination. Prior to start of a school-based typhoid vaccination program, interviews were conducted with staff of educational institutions in two townships of Karachi, Pakistan to collect baseline information about the school system and to plan a typhoid vaccination program. Data collection teams administered a structured questionnaire to all schools …

Patent Landscape Of Influenza A Virus Prophylactic Vaccines And Related Technologies, Jon R. Cavicchi, Stanley P. Kowalski, David L. Pflugh, Jeremy Barton, Jeffrey Janovetz, John Schroeder

Law Faculty Scholarship

Executive Summary: This report focuses on patent landscape analysis of technologies related to prophylactic vaccines targeting pandemic strains of influenza. These technologies include methods of formulating vaccine, methods of producing of viruses or viral subunits, the composition of complete vaccines, and other technologies that have the potential to aid in a global response to this pathogen. The purpose of this patent landscape study was to search, identify, and categorize patent documents that are relevant to the development of vaccines that can efficiently promote the development of protective immunity against pandemic influenza virus strains.

The search strategy used keywords which the …

Membrane-Bound Immunomodulators As Adjuvants In A Cell Culture-Based Avian Influenza Vaccine, David Daniel Fischer

Wayne State University Dissertations

Inactivated viral vaccines often generate suboptimal immune responses. Adjuvants are incorporated into vaccines to increase their immunogenicity, however currently available adjuvants have shortcomings which have limited their use in human and veterinary medicine. This necessitates the development of new adjuvants and delivery systems. Cytokines have been extensively tested as adjuvants in vaccines but challenges such as diffusion from antigen, short half-lives and production costs have been encountered. To address this, we developed a technology that efficiently produces inactivated, whole-virus influenza vaccine bearing membrane-bound cytokines. Tethering the cytokine to the antigen of interest keeps the immunomodulator in close contact with the …

A Comparison Of Methods For Estimating Raccoon Abundance: Implications For Disease Vaccination Programs, James C. Beasley, William S. Beatty, Todd C. Atwood, Shylo R. Johnson, Olin E. Rhodes Jr.

United States Department of Agriculture Wildlife Services: Staff Publications

Accurate estimates of demographic parameters are critical to the management of wildlife populations, including management programs focused on controlling the spread of zoonotic diseases. Rabies managers in the United States Department of Agriculture (USDA) have applied a simple raccoon (Procyon lotor) abundance index (RAI) based on cumulative catch of unique raccoons per unit area to determine vaccine-bait distribution densities. This approach was designed to allow for both the collection of biological samples and to index raccoon abundance to determine bait densities for oral rabies programs. However, postbaiting surveillance data indicate that, on average, only 30% of raccoons sampled …

The Technological Edge, Elizabeth I. Winston

Scholarly Articles

To grant a patent to natural phenomena hinders innovation, taking back from the public that which the public has a right to possess. To deny a patent to man’s manufacture undercuts the fundamental bargain of the patent system. All inventions, at their core, may be deemed natural, rendering it difficult to distinguish between man’s manufacture and natural phenomena. Determining whether the innovative aspect of the product is a technological one, rather than a natural one, can clarify whether the patent grant promotes the progress of science and the useful arts. The higher the level of skill in the art required …

Therapeutic Peptide-Based Vaccination Strategies Against Hpv-Induced Cancers, Kelly Barrios Marrugo

USF Tampa Graduate Theses and Dissertations

There is an urgent need for the development of an effective therapeutic vaccine against cancer caused by human papilloma virus (HPV). We focused on HPV-induced malignancies because of their high worldwide prevalence (e.g., cervical carcinoma and head & neck cancer). A successful therapeutic vaccine could prevent the 250 000 deaths/year worldwide and the 2.25 billion dollars that

are expended in related care in the US.

We used an HPV-induced mouse cancer model to test vaccines

composed of a CD8 T cell peptide epitope administered with potent adjuvants designed to generate vast numbers of high avidity cytotoxic T lymphocytes specific for …

Vaccine-Preventable Diseases And Foreign-Born Populations, Marc Altshuler, Md, Giang Nguyen, Md

Department of Family & Community Medicine Faculty Papers

Foreign-born individuals account for over 12% of the U.S. population, according to the most recent census data. Since many vaccine-preventable outbreaks in the U.S. have been correlated with disease importation, Congress has mandated vaccinations for numerous immigrant populations. It is essential for primary care physicians to be knowledgeable on the unique immunization-related needs of foreign-born individuals, to recognize some of the cultural and linguistic challenges that immigrants have accessing healthcare, and remember to use each medical encounter as an opportunity to provide necessary vaccinations.

Interferons As Therapeutic Agents In Infectious Diseases, Mckenzie C. Ferguson, Scott Bergman, Cathy Santanello

Pharmacy Faculty Research, Scholarship, and Creative Activity

This article explains the rationale for development of interferons as therapeutic agents, and describes commercial products available today. It also provides a summary of studies that have been performed with interferons for use as exogenous biological response modifiers in viral infections. Overall, the best data exist for treatment of viral hepatitis B and C, for which interferons are a cornerstone of therapy. Although infections with human papillomavirus and common cold viruses sometimes respond favorably to interferons, their outcomes are far from ideal. Finally, the role of interferons as vaccine adjuvants is still being explored but could be promising.