Esser-Kahn Group: Publications Latest

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Preprints

  1. Immune potentiator for increased safety and improved protection of vaccines by NF-kB modulation,” Brittany A Moser, Rachel C Steinhardt, Yoseline Escalante-Buendia, David A Bolt, Kaylynn M Barker, Stan Yoo, Bethany G McGonnigal, Aaron P Esser-Kahn. bioRxiv,

    Overview

    Many modern vaccines include adjuvants that activate the immune system and provide an enhanced humoral or cellular response. Current approved adjuvants are unable to provide desired responses against some pathogens (e.g. HIV or dengue). Many new adjuvants have been developed and demonstrate promising results, but side effects from the inflammatory response induced by these adjuvants have resulted in limited FDA approvals. No adjuvants yet possess the capability to independently modulate inflammation and protection. Here we demonstrate a method to limit inflammation and side effects associated with vaccination while retaining the protective responses using a variety of promising adjuvants. To accomplish this, we combined a selective NF-kB inhibitor with the immune adjuvant. The resulting vaccines reduce systemic inflammation and boost antibody responses. In an influenza challenge model, we demonstrate that this approach enhances protection. This method is generalizable across a broad range of adjuvants and antigens. We anticipate these studies will lead to a novel approach to vaccine formulation design that may prove general across a wide range of adjuvants, enabling their greater use in the public realm.

Recent Publications

  1. Immune potentiator for increased safety and improved protection of vaccines by NF-kB modulation,” Brittany A Moser, Rachel C Steinhardt, Yoseline Escalante-Buendia, David A Bolt, Kaylynn M Barker, Stan Yoo, Bethany G McGonnigal, Aaron P Esser-Kahn. bioRxiv,

    Overview

    Many modern vaccines include adjuvants that activate the immune system and provide an enhanced humoral or cellular response. Current approved adjuvants are unable to provide desired responses against some pathogens (e.g. HIV or dengue). Many new adjuvants have been developed and demonstrate promising results, but side effects from the inflammatory response induced by these adjuvants have resulted in limited FDA approvals. No adjuvants yet possess the capability to independently modulate inflammation and protection. Here we demonstrate a method to limit inflammation and side effects associated with vaccination while retaining the protective responses using a variety of promising adjuvants. To accomplish this, we combined a selective NF-kB inhibitor with the immune adjuvant. The resulting vaccines reduce systemic inflammation and boost antibody responses. In an influenza challenge model, we demonstrate that this approach enhances protection. This method is generalizable across a broad range of adjuvants and antigens. We anticipate these studies will lead to a novel approach to vaccine formulation design that may prove general across a wide range of adjuvants, enabling their greater use in the public realm.

  2. Applications of Immunomodulatory Immune Synergies to Adjuvant Discovery and Vaccine Development,” Janine K. Tom, Tyler J. Albin, Saikat Manna, Brittany A. Moser, Rachel C. Steinhardt, Aaron P. Esser-Kahn. Trends in Biotechnology,

    Overview

    Vaccines are some of the most successful therapies available to prevent infection. Immune synergies are being applied as tools for novel adjuvant design to improve vaccine efficacy. Next-generation synergistic adjuvants are being developed because many current adjuvants suffer from systemic toxicity or low potency.

    Novel technologies are being developed that examine synergistic interactions and enhance adjuvanticity to develop more potent and effective adjuvants. New approaches, including high-throughput screening, can provide more rapid analyses, dose sparing, and targeted delivery of vaccines.

    Targeting specific cellular compartments and cell subsets with adjuvants are emerging as ways to provide more directed immune responses. In addition, controlling the kinetic profile and robustness of the immune response has been shown to be an important factor for synergistic vaccine efficacy.

  3. “Bio-inspired counter-current multiplier for enrichment of solutes,” Kyle Brubaker, Armand Garewal, Rachel C. Steinhardt & Aaron P. Esser-Kahn. Nature Communications, 9, 2018

  4. Toll-like Receptor Agonist Conjugation: A Chemical Perspective,” Bob J. Ignacio, Tyler J. Albin, Aaron P. Esser-Kahn, and Martijn Verdoes. Bioconjugate Chemistry, 2018

  5. Cooperative CO2 Absorption Isotherms from a Bifunctional Guanidine and Bifunctional Alcohol,” Rachel Steinhardt, Stanley C. Hiew, Hemakesh Mohapatra, Du Nguyen, Zachary Oh, Richard Truong, and Aaron Esser-Kahn. ACS Central Science,

  6. Photothermal Nanoparticle Initiation Enables Radical Polymerization and Yields Unique, Uniform Microfibers with Broad Spectrum Light,” Rachel Steinhardt, Timothy Steeves, Brooke Wallace, Brittany Moser, Dmitry Fishman, and Aaron Esser-Kahn. ACS Applied Materials & Interfaces,

  7. “Light Guided In-vivo Activation of Innate Immune Cells with Photocaged TLR 2/6 Agonist,” Keun Ah Ryu, Bethany McGonnigal, Troy Moore, Tawnya Kargupta, Rock J. Mancini, and Aaron P. Esser-Kahn. Scientific Reports, 7,

  8. “Polyelectrolyte-Enrobed Cancer Cells in View of Personalized Immune-Therapy,” Lien Lybaert, Keun Ah Ryu, Riet De Rycke, Alfred C. Chon, Olivier De Wever, Karim Y. Vermaelen, Aaron Esser-Kahn, and Bruno G. De Gees. Advanced Science, 4, 2017

  9. Cancer Cell Lysate Entrapment in CaCO3 Engineered with Polymeric TLR-Agonists: Immune-Modulating Microparticles in View of Personalized Antitumor Vaccination,” Lien Lybaert, Keun Ah Ryu, Lutz Nuhn, Riet De Rycke, Olivier De Wever, Alfred Chon, Aaron Esser-Kahn, and Bruno De Geest. Chemistry of Materials, 29, 4209-4217, 2017

  10. A Photoactivatable Innate Immune Receptor for Optogenetic Inflammation,” Brittany Moser and Aaron Esser-Kahn. ACS Chemical Biology, 12, 347-350, 2017

  11. Surface Coating of Nanoparticles Reduces Background Inflammatory Activity while Increasing Particle Uptake and Delivery,” Brittany Moser, Rachel Steinhardt, and Aaron Esser-Kahn. ACS Biomaterials, 3, 206-213, 2017

  12. “Mechanically controlled radical polymerization initiated by ultrasound,” Hemakesh Mohapatra, Maya Kleiman & Aaron Palmer Esser-Kahn. Nature Chemistry, 9, 135-139, 2017

  13. Immune Response Modulation of Conjugated Agonists with Changing Linker Length,” Keun Ah Ryu, Katarzyna Slowinska, Troy Moore, and Aaron Esser-Kahn. ACS Chemical Biology, 11, 3347-3352, 2016

  14. “Development of a tri-agonist compound library used to determine optimal adjuvanticity of a Q fever vaccine,” Janine Tom, Tyler Albin, Amanda Burkhardt, Philip Felgner and Aaron Esser-Kahn. The Journal of Immunology, 196, 2016

  15. “Surface modification of carbon black nanoparticles enhances photothermal separation and release of CO2,” Samantha Goetz, Du Nguyen, Aaron Esser-Kahn. Carbon, 105, 126-135, 2016

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