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Full-Text Articles in Biomedical Engineering and Bioengineering

Interleukin-1 Alpha Increases Anti-Tumor Efficacy Of Cetuximab In Head And Neck Squamous Cell Carcinoma, Madelyn Espinosa-Cotton, Samuel N. Rodman Iii, Kathleen A. Ross, Isaac J. Jensen, Kenley Sangodeyi-Miller, Ayana J. Mclaren, Rachel A. Dahl, Katherine N. Gibson-Corley, Adam T. Koch, Yang-Xin Fu, Vladimir P. Badovinac, Douglas Laux, Balaji Narasimhan, Andrean L. Simons Jan 2019

Interleukin-1 Alpha Increases Anti-Tumor Efficacy Of Cetuximab In Head And Neck Squamous Cell Carcinoma, Madelyn Espinosa-Cotton, Samuel N. Rodman Iii, Kathleen A. Ross, Isaac J. Jensen, Kenley Sangodeyi-Miller, Ayana J. Mclaren, Rachel A. Dahl, Katherine N. Gibson-Corley, Adam T. Koch, Yang-Xin Fu, Vladimir P. Badovinac, Douglas Laux, Balaji Narasimhan, Andrean L. Simons

Chemical and Biological Engineering Publications

Background: Despite the high prevalence of epidermal growth factor receptor (EGFR) overexpression in head and neck squamous cell carcinomas (HNSCCs), incorporation of the EGFR inhibitor cetuximab into the clinical management of HNSCC has not led to significant changes in long-term survival outcomes. Therefore, the identification of novel therapeutic approaches to enhance the clinical efficacy of cetuximab could lead to improved long-term survival for HNSCC patients. Our previous work suggests that EGFR inhibition activates the interleukin-1 (IL-1) pathway via tumor release of IL-1 alpha (IL-1α), although the clinical implications of activating this pathway are unclear in the context of cetuximab therapy ...


Hemagglutinin-Based Polyanhydride Nanovaccines Against H5n1 Influenza Elicit Protective Virus Neutralizing Titers And Cell-Mediated Immunity, Kathleen Alaine Ross, Hyelee Park Loyd, Wuwei Wu, Lucas Mark Huntimer, Shaheen Ahmed, Anthony Sambol, Scott Broderick, Zachary Flickinger, Krishna Rajan, Tatiana Bronich, Surya K. Mallapragada, Michael J. Wannemuehler, Susan Long Carpenter, Balaji Narasimhan Jan 2015

Hemagglutinin-Based Polyanhydride Nanovaccines Against H5n1 Influenza Elicit Protective Virus Neutralizing Titers And Cell-Mediated Immunity, Kathleen Alaine Ross, Hyelee Park Loyd, Wuwei Wu, Lucas Mark Huntimer, Shaheen Ahmed, Anthony Sambol, Scott Broderick, Zachary Flickinger, Krishna Rajan, Tatiana Bronich, Surya K. Mallapragada, Michael J. Wannemuehler, Susan Long Carpenter, Balaji Narasimhan

Chemical and Biological Engineering Publications

H5N1 avian influenza is a significant global concern with the potential to become the next pandemic threat. Recombinant subunit vaccines are an attractive alternative for pandemic vaccines compared to traditional vaccine technologies. In particular, polyanhydride nanoparticles encapsulating subunit proteins have been shown to enhance humoral and cell-mediated immunity and provide protection upon lethal challenge. In this work, a recombinant H5 hemagglutinin trimer (H53) was produced and encapsulated into polyanhydride nanoparticles. The studies performed indicated that the recombinant H53 antigen was a robust immunogen. Immunizing mice with H53 encapsulated into polyanhydride nanoparticles induced high neutralizing antibody titers and enhanced CD4+ T ...


A Systems Approach To Designing Next Generation Vaccines: Combining α-Galactose Modified Antigens With Nanoparticle Platforms, Yashdeep Phanse, Brenda Rocio Carrillo-Conde, Amanda Ellen Ramer-Tait, Scott Broderick, Chang Sun Kong, Krishna Rajan, Ramon Flick, Robert B. Mandell, Balaji Narasimhan, Michael J. Wannemuehler Jan 2014

A Systems Approach To Designing Next Generation Vaccines: Combining α-Galactose Modified Antigens With Nanoparticle Platforms, Yashdeep Phanse, Brenda Rocio Carrillo-Conde, Amanda Ellen Ramer-Tait, Scott Broderick, Chang Sun Kong, Krishna Rajan, Ramon Flick, Robert B. Mandell, Balaji Narasimhan, Michael J. Wannemuehler

Chemical and Biological Engineering Publications

Innovative vaccine platforms are needed to develop effective countermeasures against emerging and re-emerging diseases. These platforms should direct antigen internalization by antigen presenting cells and promote immunogenic responses. This work describes an innovative systems approach combining two novel platforms, αGalactose (αGal)-modification of antigens and amphiphilic polyanhydride nanoparticles as vaccine delivery vehicles, to rationally design vaccine formulations. Regimens comprising soluble αGal-modified antigen and nanoparticle-encapsulated unmodified antigen induced a high titer, high avidity antibody response with broader epitope recognition of antigenic peptides than other regimen. Proliferation of antigen-specific CD4 + T cells was also enhanced compared to a traditional ...


Combinatorial Evaluation Of In Vivo Distribution Of Polyanhydride Particle-Based Platforms For Vaccine Delivery, Latrisha K. Petersen, Lucas Mark Huntimer, Katharine Walz, Amanda Ellen Ramer-Tait, Michael J. Wannemuehler, Balaji Narasimhan Jan 2013

Combinatorial Evaluation Of In Vivo Distribution Of Polyanhydride Particle-Based Platforms For Vaccine Delivery, Latrisha K. Petersen, Lucas Mark Huntimer, Katharine Walz, Amanda Ellen Ramer-Tait, Michael J. Wannemuehler, Balaji Narasimhan

Chemical and Biological Engineering Publications

Several challenges are associated with current vaccine strategies, including repeated immunizations, poor patient compliance, and limited approved routes for delivery, which may hinder induction of protective immunity. Thus, there is a need for new vaccine adjuvants capable of multi-route administration and prolonged antigen release at the site of administration by providing a depot within tissue. In this work, we designed a combinatorial platform to investigate the in vivo distribution, depot effect, and localized persistence of polyanhydride nanoparticles as a function of nanoparticle chemistry and administration route. Our observations indicated that the route of administration differentially affected tissue residence times. All ...


Design Of A Protective Single-Dose Intranasal Nanoparticle-Based Vaccine Platform For Respiratory Infectious Diseases, Bret Daniel Ulery, Devender Kumar, Amanda Ellen Ramer-Tait, Dennis W. Metzger, Michael J. Wannemuehler, Balaji Narasimhan Jan 2011

Design Of A Protective Single-Dose Intranasal Nanoparticle-Based Vaccine Platform For Respiratory Infectious Diseases, Bret Daniel Ulery, Devender Kumar, Amanda Ellen Ramer-Tait, Dennis W. Metzger, Michael J. Wannemuehler, Balaji Narasimhan

Chemical and Biological Engineering Publications

Despite the successes provided by vaccination, many challenges still exist with respect to controlling new and re-emerging infectious diseases. Innovative vaccine platforms composed of adaptable adjuvants able to appropriately modulate immune responses, induce long-lived immunity in a single dose, and deliver immunogens in a safe and stable manner via multiple routes of administration are needed. This work describes the development of a novel biodegradable polyanhydride nanoparticle-based vaccine platform administered as a single intranasal dose that induced long-lived protective immunity against respiratory disease caused by Yesinia pestis, the causative agent of pneumonic plague. Relative to the responses induced by the recombinant ...


Rational Design Of Pathogen-Mimicking Amphiphilic Materials As Nanoadjuvants, Bret Daniel Ulery, Latrisha K. Petersen, Yashdeep Phanse, Chang Sun Kong, Scott Broderick, Devender Kumar, Amanda Ellen Ramer-Tait, Brenda Rocio Carrillo-Conde, Krishna Rajan, Michael J. Wannemuehler, Bryan H. Bellaire, Dennis W. Metzger, Balaji Narasimhan Jan 2011

Rational Design Of Pathogen-Mimicking Amphiphilic Materials As Nanoadjuvants, Bret Daniel Ulery, Latrisha K. Petersen, Yashdeep Phanse, Chang Sun Kong, Scott Broderick, Devender Kumar, Amanda Ellen Ramer-Tait, Brenda Rocio Carrillo-Conde, Krishna Rajan, Michael J. Wannemuehler, Bryan H. Bellaire, Dennis W. Metzger, Balaji Narasimhan

Chemical and Biological Engineering Publications

An opportunity exists today for cross-cutting research utilizing advances in materials science, immunology, microbial pathogenesis, and computational analysis to effectively design the next generation of adjuvants and vaccines. This study integrates these advances into a bottom-up approach for the molecular design of nanoadjuvants capable of mimicking the immune response induced by a natural infection but without the toxic side effects. Biodegradable amphiphilic polyanhydrides possess the unique ability to mimic pathogens and pathogen associated molecular patterns with respect to persisting within and activating immune cells, respectively. The molecular properties responsible for the pathogen-mimicking abilities of these materials have been identified. The ...


Molecular Design Of Nanoparticle-Based Delivery Vehicles For Pneumonic Plague, Bret Daniel Ulery Jan 2010

Molecular Design Of Nanoparticle-Based Delivery Vehicles For Pneumonic Plague, Bret Daniel Ulery

Graduate Theses and Dissertations

The work described in this dissertation focuses on the design of polyanhydride nanoparticles that function as both adjuvants and long-term antigen delivery vehicles in order to improve vaccination, specifically for biodefense-related applications. Chapter 1 is an introduction into the threat of bioterrorism, polymer-based controlled delivery systems and challenges associated with vaccine design.

Chapter 2 is a detailed literature review of topics related to the research conducted in this dissertation. Areas covered include basic immunology, vaccine design, degradable polymer-based adjuvant engineering, plague (Yersinia pestis) biology, and vaccines that confer protection against plague.

Chapter 3 overviews the research objectives and the specific ...


Pegylation Of Niosomes, John A. Elliott Nov 2009

Pegylation Of Niosomes, John A. Elliott

Graduate Theses and Dissertations

The research presented in this dissertation describes the creation and characterization of a novel antibody-vesicle conjugate modified with polyethylene glycol (PEG) that possesses enhanced binding to and uptake by inflammation-activated endothelial cells with improved storage stability and longer shelf-life and potential reduction in immunogenic potential compared to previous designs.

Targeted drug delivery provides an effective means of delivering therapeutic concentrations of a drug to the site or organ of action. The drug is delivered using a niosome, a vesicle with an aqueous core and a bilayer membrane composed of non-ionic surfactants and cholesterol. Antibodies that recognize specific cell antigens are ...