Publications by authors named "Marie Beitelshees"

Our world is ever evolving and interconnected, creating constant opportunities for disease outbreaks and pandemics to occur, making pandemic preparedness and pathogen management crucial for global health security. Early pathogen identification and intervention play a key role in mitigating the impacts of disease outbreaks. In this perspective, we present the Viral Trait Assessment for Pandemics (ViTAP) model to aid in the early identification of high-risk viruses that have pandemic potential, which incorporates lessons from past pandemics, including which key viral characteristics are important such as genetic makeup, transmission modes, mutation rates, and symptom severity.

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Health equity is a concept that has gained increasing attention and relevance in the context of the COVID-19 pandemic, which has exposed and exacerbated the health disparities and inequities among different population groups in the United States. This article aims to provide a comprehensive and critical overview of the historical, theoretical, and empirical foundations of health equity, as well as the challenges and opportunities for advancing it in the modern US society. By adopting an interdisciplinary and intersectional approach, and by drawing on literature from public health, sociology, economics, and human rights, we argue that health equity is not only a matter of fairness and justice, but also a strategic and pragmatic goal for improving the health and well-being of the entire nation.

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Influenza still poses a significant challenge due to its high mutation rates and the low effectiveness of traditional vaccines. At present, antibodies that neutralize the highly variable hemagglutinin antigen are a major driver of the observed variable protection. To decipher how influenza vaccines can be improved, an analysis of licensed vaccine platforms was conducted, contrasting the strengths and limitations of their different mechanisms of protection.

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Recent global events have drawn into focus the diversity of options for combatting disease across a spectrum of prophylactic and therapeutic approaches. The recent success of the mRNA-based COVID-19 vaccines has paved the way for RNA-based treatments to revolutionize the pharmaceutical industry. However, historical treatment options are continuously updated and reimagined in the context of novel technical developments, such as those facilitated through the application of synthetic biology.

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In this opening chapter, we outline the basics of vaccine delivery and subsequent immune reactivity. Vaccine delivery is an augmentation to immunization more generally in that a delivery reagent is harnessed to improve administration of the key ingredient (i.e.

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The enclosed work focuses on the construction variables associated with a dual-antigen liposomal carrier, delivering encapsulated polysaccharides and surface-localized proteins, which served as a vaccine delivery device effective against pneumococcal disease. Here, the goal was to better characterize and compare the carrier across a range of formulation steps and assessment metrics. Specifically, the vaccine carrier was subjected to new methods of liposomal formation, including alterations to the base components used for subsequent macromolecule encapsulation and surface attachment, with characterization spanning polysaccharide encapsulation, liposomal size and charge, and surface protein localization.

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A hybrid biological-biomaterial antigen delivery vector comprised of a polymeric shell encapsulating an core was previously developed for antigen production and subsequent delivery. Due to the engineering capacity of the bacterial core, the hybrid vector provides unique opportunities for immunogenicity optimization through varying cellular localization (cytoplasm, periplasm, cellular surface) and type (protein or DNA) of antigen. In this work, three protein-based hybrid vector formats were compared in which the pneumococcal surface protein A (PspA) was localized to the cytoplasm, surface, and periplasmic space of the bacterial core for vaccination against pneumococcal disease.

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We detail the development of a next-generation Streptococcus pneumoniae liposomal encapsulation of polysaccharides (LEPS) vaccine, with design characteristics geared toward best-in-class efficacy. The first generation LEPS vaccine, which contained 20 encapsulated pneumococcal capsular polysaccharides (CPSs) and two surface-displayed virulence-associated proteins (GlpO and PncO), enabling prophylactic potency against 70+ serotypes of Streptococcus pneumoniae (the causative agent of pneumococcal disease), was rationally redesigned for advanced clinical readiness and best-in-class coverage. In doing so, the virulent-specific GlpO protein antigen was removed from the final formulation due to off-target immunogenicity toward bacterial species within the human microbiome, while directed protection was maintained by increasing the dose of PncO from 17 to 68 μg.

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Various bacterial species cycle between growth phases and biofilm formation, of which the latter facilitates persistence in inhospitable environments. These phases can be generally characterized by one or more cellular phenotype(s), each with distinct virulence factor functionality. In addition, a variety of phenotypes can often be observed within the phases themselves, which can be dependent on host conditions or the presence of nutrient and oxygen gradients within the biofilm itself (i.

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Over time, there has been a growing interest in the application of gene therapy within the healthcare industry as demonstrated by the nearly 3,000 clinical trials associated with gene therapy that are listed in clinicaltrials.gov. However, there are various difficulties associated with gene therapy that have limited the realization of licensed gene therapies to only a handful of treatments.

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Commensal organisms with the potential to cause disease pose a challenge in developing treatment options. Using the example featured in this study, pneumococcal disease begins with colonization, followed by triggering events that prompt the release of a virulent subpopulation of bacteria. Current vaccines focus on colonization prevention, which poses unintended consequences of serotype niche replacement.

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Photodynamic therapy (PDT) and gene delivery have both been used to target both cancer cells and tumor-associated macrophages (TAMs). Given the complex nature of tumor tissue, there could be merit in combining these strategies simultaneously. In this study, we developed a bimodal targeting approach to both cancer cells and macrophages, employing materials conducive to both gene delivery and PDT.

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The type and potency of an immune response provoked during vaccination will determine ultimate success in disease prevention. The basis for this response will be the design and implementation of antigen presentation to the immune system. Whereas direct antigen administration will elicit some form of immunological response, a more sophisticated approach would couple the antigen of interest to a vector capable of broad delivery formats and designed for heightened response.

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Immunization strategies against commensal bacterial pathogens have long focused on eradicating asymptomatic carriage as well as disease, resulting in changes in the colonizing microflora with unknown future consequences. Additionally, current vaccines are not easily adaptable to sequence diversity and immune evasion. Here, we present a "smart" vaccine that leverages our current understanding of disease transition from bacterial carriage to infection with the pneumococcus serving as a model organism.

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Vaccines stand as a very powerful means of disease prevention and treatment. Fundamental to the success of vaccination is the efficient delivery of antigenic cargo needed to trigger an effective immune response. In this article, we will review recent advances in delivery technology with a focus on devices designed to optimally maximize responses to antigen cargo.

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