Browsing by Subject "Vaccines"

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    Cost-Effectiveness Analysis of Hepatitis A Vaccination in Contrasting Economic Environments
    (2018-12) Ghildayal, Nidhi
    Hepatitis A is one of the most common vaccine-preventable diseases. The virus is one of the greatest causes of foodborne infection, with epidemics often rapidly spreading through food and water sources. In its most severe cases, the disease can result in the need for a liver transplant or death. Complications can include recurring symptoms over several months. Most commonly, the disease causes a great amount of lost productivity and medical costs (WHO, 2010). In today’s rapidly changing world, many economies are developing quickly and countries are experiencing higher levels of sanitation, resulting in an epidemiological shift of the hepatitis A virus in many locations. The epidemiological shift occurs when children avoid being infected with the disease until a later age due to cleaner water sources, food, and hygiene practices in their environment; but if and when they are infected at this later age, the disease is much more severe and lost productivity costs are higher (Lopez et al, 2007). A hepatitis A vaccine exists, yet remains underutilized throughout much of the world (WHO, 2010). The vast number of hepatitis A cases, as well as the looming potential severity of an increasing average age of infection in many regions, creates a need for an evaluation of current hepatitis A vaccination strategies to ensure that those that are being implemented are most beneficial to society. Hepatitis A vaccination recommendations are often outdated or nonexistent. Several developed nations have vaccination strategies that target high-risk groups or children who live in areas with high incidence rates of the disease (Armstrong et al, 2007), but often fail to routinely reevaluate vaccination strategies once universal vaccination policies have been put in place (Plotkin et al, 2013). This is despite the cyclical nature of hepatitis A, which generally has a large increase in incidence every ten years, followed by a decrease to a rate lower than the previous baseline incidence (Fiore, 2004). With very few exceptions, developing countries generally have no recommendations and sparse resources dedicated to research on the disease (Quezada et al, 2008). In order to determine the strategies that will currently be most beneficial in terms of quality-adjusted life years (QALYs) and cost, I have created a model and conducted a cost-effectiveness analysis to investigate vaccination recommendation strategies in a More Economically Developed Country (MEDC), commonly known as a “developed” area, the United States, and a Less Economically Developed Country (LEDC), commonly known as a “developing” area, or in this case, the state of Rio de Janeiro, Brazil. In 2009, and currently, these two areas had different vaccination strategies for hepatitis A. The model ran two different scenarios – in the USA, I modeled the universal vaccination policy and what it would look like if it was taken away, and in Rio de Janeiro, I modeled no vaccination, as well as what it would look like if a universal vaccination policy was implemented. I have also conducted an analysis to show, if this epidemiological shift of the disease continues in these regions, what type of future burden hepatitis A may have in a hypothetical rapidly-developing country.
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    Identifying Mechanisms And Biomarkers Predictive Of Efficacy Of Vaccines Against Opioid Use Disorders And Overdose
    (2022-08) Crouse, Bethany
    Opioid use disorders (OUD) and overdose are public health crises that are worsening despite the availability of approved pharmacotherapies. Active immunization with anti-opioid conjugate vaccines is a novel therapeutic strategy to treat OUD and prevent overdose. To date, clinical studies suggest that efficacy of anti-drug conjugate vaccines is limited to a subset of individuals who can produce optimal antibody responses. To increase positive treatment outcomes and clinical success, this research program investigated several complementary strategies to increase OUD vaccine efficacy. First, mechanisms of optimal anti-opioid vaccine response are investigated by elucidating the immunological mechanisms behind a previously established interleukin-4 (IL-4) mediated increase in vaccine efficacy. These studies found that depletion of IL-4 resulted in a Type I IL-4R mediated increase in germinal center formation and germinal center T cell response which leads to increased opioid-specific antibody secreting cells, and that vaccine efficacy is dependent on a balanced Th1/Th2 T cell response in mice. Next, these results provided a blueprint for next generation anti-fentanyl vaccine formulations incorporating novel adjuvants targeting toll-like receptors (TLRs). These data show that a TLR7/8 agonist adjuvant increases vaccine efficacy in rodent and porcine models of fentanyl misuse and overdose. Third, vaccine design and immunization paradigms were assessed to optimize the efficacy of a novel carfentanil vaccine alone and in combination with a lead fentanyl vaccine. Longer linker lengths and a co-administered bivalent immunization strategy were associated with increased vaccine efficacy. Then, environmental factors contributing to the immune response are investigated by testing whether changes in the gastrointestinal microbiome would affect vaccine efficacy and whether these specific changes in the microbiome could be utilized as biomarkers. These studies revealed that changes in the microbiome in specific pathogen free or immune-experienced rodents did not affect efficacy of anti-oxycodone or anti-fentanyl vaccines. Finally, exploratory studies were performed to identify putative biomarkers that may be predictive of anti-opioid vaccine response in preclinical and clinical investigations. These studies indicate that pre-immunization concentration of IL-4 is correlated with vaccine efficacy in genetically diverse mice, and that specific cytokines may be of interest as indicators of immune response in human patients. Overall, the findings outlined in this research program support the use of novel adjuvants and predictive biomarkers to increase clinical efficacy of vaccines to treat OUD and overdose.