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Aluminum Adjuvants In Vaccines: Movement Towards Understanding Their Role And Mechanism Of Action, Thad Rehmert

BIO 410 Spring 2019 Research Papers

Aluminum adjuvants have been used in vaccines for over 80 years in order to increase the immune response in vaccinated individuals. While the addition of aluminum adjuvants has been extremely successful, the success powered the adjuvants to be used in numerous vaccines without a proper understanding of their mechanisms of action. Advancements in medical understanding over the last 4-5 decades has resulted in researchers understanding the harsh reality of aluminum toxicity. Due to this, researchers have begun to delve into the actions and mechanisms of these adjuvants in an effort to enhance understanding of how they work. This review will …

Preparation And Evaluation Of Single-Stranded Dna Aptamer-Based Immunological Adjuvant In Broiler Chickens, Adil Sabr Al-Ogaili

Graduate Theses and Dissertations

Mineral oils and metal salts are commonly used as adjuvants to enhance acquired immunity. Recently, monoclonal antibodies (MAbs) and recombinant peptides agonist CD40 receptor have shown remarkable promise for induction of rapid and robust immune responses. Limitations of this approach MAb production costs and multiple administrations due to anti-MAb immune responses. Here we demonstrate the development of a unique and sophisticated DNA aptamer-based alternative for CD40-directed delivery of universal antigens as an alternative in chickens, and potentially other vertebrate species. This receptor, expressed by antigen-presenting cells, acts as a costimulatory molecule for activated T helper lymphocytes. After initially selecting for …

Implementation Of The Vaccines For Children Program In A Midwest, Urban Clinic Dedicated To The Underserved Population, Akmal Saydazamov

Doctoral Projects

Background: Low immunization rates weaken herd immunity and endanger children. The Safety Net Health Clinic (SNHC) study site serves an underprivileged and refugee population with significantly lower than ideal coverage. Series completion disparities persisted after control for demographic, access-to-care, poverty and language effects (Varan et al, 2016).

Objectives: SNHC implemented the Vaccines for Children (VFC) program in order to increase the vaccination rates among the underserved population.

Methods: As an efficacy study, the project focused on three major areas in the VFC implementation – cost, staff preparedness and patient need. Cost was determined by utilizing electronic medical records (EMR) and …

The Deadly Influenza Virus And Its Changing Forms, Kayce Boggess

D.U.Quark

The influenza virus has plagued humans for centuries. Recently antiviral medications, which shorten the duration of the flu, have been introduced into society. These medications along with vaccinations, which try to give the body immunity before the virus strikes, help to stop the flu before it attacks the host. The virus, however, replicates using host cells and can slightly change itself with each replication, which over time could lead to a strain immune to the current antiviral medication and vaccines. However, using more preventative measures could help slow the changing strains of the flu virus. Using vaccines to stop the …

Evaluation Of A Self-Adjuvanted Self-Assembling Protein Nanoparticle As A Platform For Vaccine Development, Sarah Low

Doctoral Dissertations

Vaccines are one of the most impactful inventions in modern medicine and are responsible for significant improvements in public health. While various vaccine types are available, subunit vaccines have substantial interest in the field. Typical subunit vaccines are advantageous because they are considered safe; however, they often do not elicit strong immune responses because they cannot crosslink B cell receptors. To overcome this, repetitive display systems are used. Here we study an exciting platform called Self-Assembling Protein Nanoparticles (SAPNs), which contain coiled-coil oligomerization domains that self-assemble into nanoparticles similar in size and shape to icosahedral viruses. Previous work has demonstrated …

A Qualitative Examination Of Vaccine Hesitancy Among Mothers, Alicia L. Benner, Annie Vasterling, Teia Wolter

All Electronic Theses and Dissertations

Vaccine hesitancy describes the reluctance to vaccinate or the delay of vaccines (World Health Organization [WHO], 2017a). Various factors contribute to vaccine hesitancy for patients (Salmon, Dudley, Glanz, & Somer, 2015), and multiple sources are used by patients to gain vaccine information (Salmon et al., 2015), making it difficult for healthcare providers to address vaccine hesitancy. This research was conducted to identify factors that cause mothers to be vaccine hesitant and information sources used to support the mothers’ vaccination beliefs. Phone interviews were conducted with twelve vaccine hesitant mothers. Participants were asked if the following factors contributed to their vaccine …

Efficacy Of A Single Dose Hpv Vaccine And Its Potential Outcomes In Low-Income Countries, Brooke Schramm

Theses and Graduate Projects

Cervical cancer is a leading worldwide cause of cancer mortality in women and disproportionately burdens low-income countries. Human papillomavirus (HPV) has been proven as the primary cause of genital warts, some oropharyngeal cancers, and anogenital cancers such as cervical, vulvar, anal, and penile malignancies. HPV vaccination coupled with regular HPV screenings are major strategies for preventing HPV infections, but with high costs and infrastructure complexities associated with current vaccination and screening programs, many world regions are unable to provide protection against HPV infection and its sequalae. If unabated, cervical cancer incidence is expected to increase worldwide over the coming decades …

Performance Differences Between Two Groups Of Commercial Pigs Following Experimental Infection With Prrs Virus 1-7-4, Erin Little

Electronic Theses and Dissertations

Porcine reproductive and respiratory syndrome virus (PRRSV) is the costliest swine disease in North America. Vaccines and management alone have not been effective in controlling this disease. Genetic selection for resilience may be a complimentary approach for controlling PRRSV. The objective of this study was to estimate performance differences between two groups of pigs from the same commercial line following infection with PRRSV 1-7-4: 1) pigs sired by boars selected based on a standard index (TN-S), which emphasized feed efficiency and carcass quality; and 2) pigs sired by boars selected based on an experimental index (TN-E), which emphasized feed intake, …

Role Of Type I Interferon (Ifn) In The Respiratory Syncytial Virus (Rsv) Immune Response And Disease Severity, Diego R. Hijano, Luan D. Vu, Lawrence M. Kauvar, Ralph A. Tripp, Fernando P. Polack, Stephania A. Cormier

Faculty Publications

© 2019 Hijano, Vu, Kauvar, Tripp, Polack and Cormier. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract disease in children patients, such as premature infants, patients with cardiac …

Vitellogenin Receptor As A Target For Tick Control: A Mini-Review, Robert D. Mitchell Iii, Daniel E. Sonenshine, Adalberto A. Pérez De León

Biological Sciences Faculty Publications

While much effort has been put into understanding vitellogenesis in insects and other organisms, much less is known of this process in ticks. There are several steps that facilitate yolk formation in developing oocytes of which the vitellogenin receptor (VgR) is a key component. The tick VgR binds vitellogenin (Vg) circulating in the hemolymph to initiate receptor-mediated endocytosis and its transformation into vitellin (Vn). The conversion of Vg into Vn, the final form of the yolk protein, occurs inside oocytes of the female tick ovary. Vn is critical to tick embryos since it serves as the nutritional source for their …

A Single-Cycle Adenovirus Type 7 Vaccine For Prevention Of Acute Respiratory Disease, Brianna L. Bullard, Brigette N. Corder, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Adenovirus type 7 (Ad7) infection is associated with acute respiratory disease (ARD), especially in military recruits living in close quarters. Recently, several outbreaks of Ad7 infections have occurred in civilian populations, with some cases leading to death. However, the current Ad7 vaccine is licensed for use only in military recruits because it utilizes an orally delivered wild type virus which is shed in the stool for 28 days after immunization. This poses a safety risk due to the possibility of virus spread to vulnerable populations. To address the need for a safer Ad7 vaccine for use in civilian populations, we …

Influenza H1 Mosaic Hemagglutinin Vaccine Induces Broad Immunity And Protection In Mice, Brigette N. Corder, Brianna L. Bullard, Jennifer L. Debeauchamp, Natalia A. Ilyushina, Richard J. Webby, Eric A. Weaver

School of Biological Sciences: Faculty Publications

Annually, influenza A virus (IAV) infects ~5–10% of adults and 20–30% of children worldwide. The primary resource to protect against infection is by vaccination. However, vaccination only induces strain-specific and transient immunity. Vaccine strategies that induce cross-protective immunity against the broad diversity of IAV are needed. Here we developed and tested a novel mosaic H1 HA immunogen. The mosaic immunogen was optimized in silico to include the most potential B and T cell epitopes (PBTE) across a diverse population of human H1 IAV. Phylogenetic analysis showed that the mosaic HA localizes towards the non-pandemic 2009 strains which encompasses the broadest …

Time Series Analysis For Effect Of Vaccines On Pneumonia Or Gastrointestinal Disorders In Brazil, Kang Shen

Public Health Theses

It is important for public health professionals to understand the effects of vaccine introduction and compare different types of vaccinations. This study will focus on understanding the pre and post vaccination effects of two different infectious diseases: pneumonia and gastrointestinal disorders. One of approaches of getting the accurate estimate of vaccine impact is by comparing rates or trends of the targeted disease in the years after introduction with rates of trend in the year before introduction using a time-series analysis. Specifically, in this study, the synthetic controls method implements an approach to estimating the causal effect of a designed intervention …

Trypanosoma Cruzi Trypomastigote Glycosylphosphatidylinositol-Anchored Mucins And A Synthetic Alpha-Gal-Containing Neoglycoprotein As Potential Biomarkers And Vaccines For Chagas Disease, Igor Leandro Estevao

Open Access Theses & Dissertations

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a neglected tropical disease that kills or permanently disable thousands of people annually. About 6-8 million people are estimated to be infected worldwide. Although many efforts have been made for the development of an effective immunotherapy, currently there is no vaccine to prevent or treat CD in humans. Despite their toxicity, the two current drugs for CD, benznidazole (BZN) and nifurtimox (NFX), have medium-to-high efficacy in the chronic stage of the disease and could save or improve the lives of thousands of patients. However, negative seroconversion in treated patients, as …

Vaccine Myths: Setting The Record Straight, Julie A. Boom, Rachel M. Cunningham, Lindy U. Mcgee

Journal of Family Strengths

Despite their standing as one of the most remarkable public health achievements, vaccines have been surrounded by dangerous myths since the development of the smallpox vaccine in the 18th century. In recent decades, with the publication of a fraudulent article linking vaccines to autism, the involvement of celebrities in the debate, and the rise of the internet and social media as sources for information for patients, these myths have become more widespread. This paper reviews four common vaccine myths: vaccines cause autism, vaccines are not safe, too many vaccines are given too soon, and the influenza vaccine is not necessary. …

Human Papillomavirus: The Influence Of Prevention And Vaccination, Lacey N. Russell

Kentucky Journal of Undergraduate Scholarship

Human Papillomavirus infections (HPV) are the most common sexually transmitted diseases in the United States. Of cancers in parts of the body where HPV is often discovered about 80% originated from an HPV infection. Despite this knowledge and the effectiveness of the HPV vaccine, vaccination by both genders in Kentucky and on a national scale remains highly underutilized. As a result, preventable incidence and mortality rates from HPV-related illness are elevated. Health care delivery factors such as increased vaccination and preventative care, insurance coverage, and accessible rural health care are necessary for HPV prevention and promotion of holistic health. The …

First Results On Survival From A Large Phase 3 Clinical Trial Of An Autologous Dendritic Cell Vaccine In Newly Diagnosed Glioblastoma, Linda M. Liau, Keyoumars Ashkan, David D. Tran, Jian L. Campian, John E. Trusheim, Charles S. Cobbs, Jason A. Heth, Michael Salacz, Sarah Taylor, Stacy D. D'Andre, Fabio M. Iwamoto, Edward J. Dropcho, Yaron A. Moshel, Kevin A. Walter, Clement P. Pillainayagam, Robert Aiken, Rekha Chaudhary, Samuel A. Goldlust, Daniela A Bota, Paul Duic, Jai Grewal, Heinrich Elinzano, Steven A. Toms, Kevin O. Lillehei, Tom Mikkelsen, Tobias Walbert, Steven R. Abram, Andrew J. Brenner, Steven Brem, Matthew G. Ewend, John L. Villano

Internal Medicine Faculty Publications

Background: Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax^®-L) to standard therapy for newly diagnosed glioblastoma.

Methods: After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS).

Results: For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months …

Evolution Of Bordetella Pertussis Genome May Play A Role In The Increased Rate Of Whooping Cough Cases In The United States, Kevin Loftus

Senior Honors Projects, 2010-2019

Bordetella pertussis is the bacterium responsible for pertussis, a disease commonly referred to as whooping cough. Recently, pertussis has made a resurgence in the U.S. despite high-vaccination coverage. Possible causes of the increased number of pertussis cases include genetic evolution of B. pertussis, increased awareness of the disease, better laboratory diagnostics, and the switch from a whole-cellular (wP) vaccine to an acellular vaccine (aP) in the 1990s. Fortunately, just as B. pertussis is evolving, so is the arsenal of technologies used to understand and combat this pathogenic bacterium. Whole genome sequencing is one technology that helps researchers better understand …

A Plant-Produced Vaccine Protects Mice Against Lethal West Nile Virus Infection Without Enhancing Zika Or Dengue Virus Infectivity, Huafang Lai, Amber M. Paul, Haiyan Sun, Junyun He, Ming Yang, Fengwei Bai

Faculty Publications

West Nile virus (WNV) has caused multiple global outbreaks with increased frequency of neuroinvasive disease in recent years. Despite many years of research, there are no licensed therapeutics or vaccines available for human use. One of the major impediments of vaccine development against WNV is the potential enhancement of infection by related flaviviruses in vaccinated subjects through the mechanism of antibody-dependent enhancement of infection (ADE). For instance, the recent finding of enhancement of Zika virus (ZIKV) infection by pre-exposure to WNV further complicates the development of WNV vaccines. Epidemics of WNV and the potential risk of ADE by current vaccine …

First Impressions—The Potential Of Altering Initial Host-Virus Interactions For Rational Design Of Herpesvirus Vaccine Vectors, Paul J.F. Rider, Farhana Musarrat, Rafiq Nabi, Shan Naidu, Konstantin G. Kousoulas

Faculty Publications

© 2018, Springer International Publishing AG, part of Springer Nature. Purpose of Review: The earliest host-virus interactions occur during virus attachment and entry into cells. These initial steps in the virus lifecycle influence the outcome of infection beyond delivery of the viral genome into the cell. Herpesviruses alter host signaling pathways and processes during attachment and entry to facilitate virus infection and modulate innate immune responses. We suggest in this review that understanding these early events may inform the rational design of therapeutic and prevention strategies for herpesvirus infection, as well as the engineering of viral vectors for immunotherapy purposes. …

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Rhodococcus Equi In The Foal – Improving Diagnostic And Prevention Measures, Fernanda Bicudo Cesar

Theses and Dissertations--Veterinary Science

Although Rhodococcus equi (R. equi), previously known as Corynebacterium equi, was first isolated from pneumonic foals almost a century ago, it remains the most common cause of subacute or chronic granulomatous bronchopneumonia in foals. While the majority of foals exposed to R. equi develop a protective immune response (regressors), others exhibit a unique susceptibility to infection (progressors). The determinants for either outcome are not completely understood. Therefore, current diagnostic and preventive measures are suboptimal and require betterment. In light of this current need, we hypothesized that immunoglobulin G subisotype T [IgG(T)] against the virulence-associated protein A (VapA) …

Evaluating Parents' Decisions Regarding Recommended Childhood Vaccinations, Jennifer Kline

Walden Dissertations and Doctoral Studies

Vaccinations are among the greatest accomplishments of public health. However, many parents are choosing not to vaccinate. The purpose of this study was to explore the association between social media influence and parents' decisions to vaccinate their children. The health belief model indicates that individuals' likelihood of engaging in a health-related behavior is determined by their perceptions of susceptibility, severity, benefits, and barriers. The research questions addressed whether there is an association between parents' perception of their children's disease susceptibility and their decisions about vaccination, and whether there is an association between exposure to messaging from social media and parents' …

Gene Expression Profiles Of The Small Intestinal Mucosa Of Dogs Repeatedly Infected With The Cestode Echinococcus Multilocularis, Hirokazu Kouguchi, Takao Irie, Jun Matsumoto, Hidefumi Furuoka, Kenji Ishiwata, Ryo Nakao, Kinpei Yagi

Harold W. Manter Laboratory of Parasitology: Library Materials

The data set presented in this article is related to a previous research article entitled, The timing of worm exclusion in dogs repeatedly infected with the cestode Echinococcus multilocularis (Kouguchi et al., 2016). This article describes the genes >2 fold up- or down-regulated in the first- and repeated-infection groups compared to the healthy controls group. The gene expression profiles were generated using the Agilent-021193 Canine (V2) Gene Expression Microarray (GPL15379). The raw and normalized microarray data have been deposited with the Gene Expression Omnibus (GEO) database under accession number GSE105098.

Surveying Host Innate Immune Responses To Interferon Antagonist-Deficient Murine Coronaviruses, Aaron Brian Volk

Master's Theses

Two coronaviruses (CoVs)—severe acute respiratory syndrome (SARS) virus and Middle East respiratory syndrome (MERS) virus—have emerged in the 21st century from animal reservoirs into the human population, each causing an epidemic associated with significant disease and mortality. CoV epidemics are currently only controllable by rigorous public health measures; no targeted therapeutics or vaccines exist to treat or prevent any human CoV infection. One method of generating attenuated CoV strains to be studied as vaccine candidates involves specifically disrupting CoV-encoded interferon (IFN) antagonists, thereby rendering the virus vulnerable to host innate antiviral immunity. Deubiquitinating (DUB) activity encoded within CoV nonstructural protein …

Working To Improve Human Papilloma Virus Vaccination Uptake In Michigan, Courtney Cole, Angela Mcfall

Michigan Journal of Public Health

Increased cases of Human Papillomavirus (HPV) related cancers and low HPV vaccine uptake are public health concerns that directly affect young adults and adolescents around the country. The HPV vaccine is recommended to prevent HPV associated cancers. Increased awareness and health education interventions are needed to promote the importance of the HPV vaccine and to achieve an HPV vaccine completion rate of 80% as outlined by the Healthy People 2020 goal. The Michigan Cancer Consortium HPV vaccine Priority Workgroup is working to improve vaccine uptake in Michigan through statewide projects that promote health education resources and address barriers associated with …

Cost-Effectiveness Analysis Of Targeted Herpes Zoster Vaccination In Adults 50-59 At Increased Cardiovascular Risk, Kathleen M. Glassner

USF Tampa Graduate Theses and Dissertations

Background: Over the last twenty years the incidence of herpes zoster (HZ) infection, also known as shingles, has been increasing among adults for unknown reasons. The economic burden of HZ is currently estimated at over $1 billion per year in the United States (U.S.) and is expected to increase as the susceptible adult population ages. HZ is caused by a re-activation of the varicella zoster virus (VZV), chicken pox, and more than 95% of adults living today carry the virus with a lifetime risk of 1 in 3 for developing HZ. In 2006 the FDA approved a vaccine for the …

In Vivo Efficacy Of A Cocktail Of Human Monoclonal Antibodies (Cl184) Against Diverse North American Bat Rabies Virus Variants, Richard Franka, William C. Carson, James A. Ellison, Steven T. Taylor, Todd G. Smith, Natalia A. Kuzmina, Ivan V. Kuzmin, Wilfred Marissen, Charles E. Rupprecht

ETSU Faculty Works

Following rabies virus (RABV) exposure, a combination of thorough wound washing, multiple-dose vaccine administration and the local infiltration of rabies immune globulin (RIG) are essential components of modern post-exposure prophylaxis (PEP). Although modern cell-culture-based rabies vaccines are increasingly used in many countries, RIG is much less available. The prohibitive cost of polyclonal serum RIG products has prompted a search for alternatives and design of anti-RABV monoclonal antibodies (MAbs) that can be manufactured on a large scale with a consistent potency and lower production costs. Robust in vitro neutralization activity has been demonstrated for the CL184 MAb cocktail, a 1:1 protein …

Peptide Vaccine Formulation Controls The Duration Of Antigen Presentation And Magnitude Of Tumor‐Specific Cd8+ T Cell Response, Hiep Khong

Dissertations and Theses (Open Access)

Despite remarkable progresses in vaccinology, therapeutic cancer vaccines have not achieved their full potential. We previously showed that the duration of antigen presentation critically affected the quantity and quality of T cell response and subsequent anti‐tumor efficacy. Here we describe L‐tyrosine amino acid‐based microparticles as a novel peptide vaccine adjuvant for the induction of tumor‐specific T cells. L‐tyrosine microparticles did not induce inflammasome activation, but instead extended antigen presentation time. The consequent prolongation in antigen presentation translated into prolonged T cell proliferation and superior numbers and anti‐tumor function of vaccination‐induced CD8+ T cells. Indeed, prolonging antigen presentation by repeated injection …

Cytomegalovirus Serostatus, Inflammation, And Antibody Response To Influenza Vaccination In Older Adults: The Moderating Effect Of Beta Blockade, Rebecca G. Reed, Richard N. Greenberg, Suzanne C. Segerstrom

Psychology Faculty Publications

Cytomegalovirus (CMV) has been implicated as a factor in immunosenescence, including poor antibody response to vaccination and higher immune activation and inflammation. Some people may be more or less vulnerable to the negative effects of CMV. The present investigation tested the effects of beta-blocker use and chronological age on the associations between CMV and immunity in adults aged 60–91 (N=98; 69% CMV seropositive) who were administered the trivalent influenza vaccine for up to 5 years. Peak antibody response, corrected for baseline, and spring (persistent) antibody response, corrected for peak, were assessed, as well as beta-2 microglobulin (β2μ) and interleukin-6 (IL-6). …