Emily Meany

All Publications

• Saponin nanoparticle adjuvants incorporating Toll-like receptor agonists drive distinct immune signatures and potent vaccine responses. Science advances Ou, B. S., Baillet, J., Filsinger Interrante, M. V., Adamska, J. Z., Zhou, X., Saouaf, O. M., Yan, J., Klich, J. H., Jons, C. K., Meany, E. L., Valdez, A. S., Carter, L., Pulendran, B., King, N. P., Appel, E. A. 2024; 10 (32): eadn7187

  Abstract

  Over the past few decades, the development of potent and safe immune-activating adjuvant technologies has become the heart of intensive research in the constant fight against highly mutative and immune evasive viruses such as influenza, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and human immunodeficiency virus (HIV). Herein, we developed a highly modular saponin-based nanoparticle platform incorporating Toll-like receptor agonists (TLRas) including TLR1/2a, TLR4a, and TLR7/8a adjuvants and their mixtures. These various TLRa-saponin nanoparticle adjuvant constructs induce unique acute cytokine and immune-signaling profiles, leading to specific T helper responses that could be of interest depending on the target disease for prevention. In a murine vaccine study, the adjuvants greatly improved the potency, durability, breadth, and neutralization of both COVID-19 and HIV vaccine candidates, suggesting the potential broad application of these adjuvant constructs to a range of different antigens. Overall, this work demonstrates a modular TLRa-SNP adjuvant platform that could improve the design of vaccines and affect modern vaccine development.

  View details for DOI 10.1126/sciadv.adn7187

  View details for PubMedID 39110802

  View details for PubMedCentralID PMC11305391

• Label-Free Composition Analysis of Supramolecular Polymer-Nanoparticle Hydrogels by Reversed-Phase Liquid Chromatography Coupled with a Charged Aerosol Detector. Analytical chemistry Tang, S., Pederson, Z., Meany, E. L., Yen, C., Swansiger, A. K., Prell, J. S., Chen, B., Grosskopf, A. K., Eckman, N., Jiang, G., Baillet, J., Pellett, J. D., Appel, E. A. 2024

  Abstract

  Supramolecular hydrogels formed through polymer-nanoparticle interactions are promising biocompatible materials for translational medicines. This class of hydrogels exhibits shear-thinning behavior and rapid recovery of mechanical properties, providing desirable attributes for formulating sprayable and injectable therapeutics. Characterization of hydrogel composition and loading of encapsulated drugs is critical to achieving the desired rheological behavior as well as tunable in vitro and in vivo payload release kinetics. However, quantitation of hydrogel composition is challenging due to material complexity, heterogeneity, high molecular weight, and the lack of chromophores. Here, we present a label-free approach to simultaneously determine hydrogel polymeric components and encapsulated payloads by coupling a reversed phase liquid chromatographic method with a charged aerosol detector (RPLC-CAD). The hydrogel studied consists of modified hydroxypropylmethylcellulose, self-assembled PEG-b-PLA nanoparticles, and a therapeutic compound, bimatoprost. The three components were resolved and quantitated using the RPLC-CAD method with a C4 stationary phase. The method demonstrated robust performance, applicability to alternative cargos (i.e., proteins) and was suitable for composition analysis as well as for evaluating in vitro release of cargos from the hydrogel. Moreover, this method can be used to monitor polymer degradation and material stability, which can be further elucidated by coupling the RPLC method with (1) a multi-angle light scattering detector (RPLC-MALS) or (2) high resolution mass spectrometry (RPLC-MS) and a Fourier-transform based deconvolution algorithm. We envision that this analytical strategy could be generalized to characterize critical quality attributes of other classes of supramolecular hydrogels, establish structure-property relationships, and provide rational design guidance in hydrogel drug product development.

  View details for DOI 10.1021/acs.analchem.3c05747

  View details for PubMedID 38567987

• A Regimen Compression Strategy for Commercial Vaccines Leveraging an Injectable Hydrogel Depot Technology for Sustained Vaccine Exposure ADVANCED THERAPEUTICS Yan, J., Ou, B. S., Saouaf, O. M., Meany, E. L., Eckman, N., Appel, E. A. 2023

  View details for DOI 10.1002/adtp.202300108

  View details for Web of Science ID 001004577500001

• Injectable Polymer-Nanoparticle Hydrogel for the Sustained Intravitreal Delivery of Bimatoprost ADVANCED THERAPEUTICS Meany, E. L., Andaya, R., Tang, S., Kasse, C. M., Fuji, R. N., Grosskopf, A. K., D'Aquino, A. L., Bartoe, J. T., Ybarra, R., Shelton, A., Pederson, Z., Hu, C., Leung, D., Nagapudi, K., Ubhayakar, S., Wright, M., Yen, C., Appel, E. A. 2022

  View details for DOI 10.1002/adtp.202200207

  View details for Web of Science ID 000876774400001

• Injectable Nanoparticle-Based Hydrogels Enable the Safe and Effective Deployment of Immunostimulatory CD40 Agonist Antibodies. Advanced science (Weinheim, Baden-Wurttemberg, Germany) Correa, S., Meany, E. L., Gale, E. C., Klich, J. H., Saouaf, O. M., Mayer, A. T., Xiao, Z., Liong, C. S., Brown, R. A., Maikawa, C. L., Grosskopf, A. K., Mann, J. L., Idoyaga, J., Appel, E. A. 2022: e2103677

  Abstract

  When properly deployed, the immune system can eliminate deadly pathogens, eradicate metastatic cancers, and provide long-lasting protection from diverse diseases. Unfortunately, realizing these remarkable capabilities is inherently risky as disruption to immune homeostasis can elicit dangerous complications or autoimmune disorders. While current research is continuously expanding the arsenal of potent immunotherapeutics, there is a technological gap when it comes to controlling when, where, and how long these drugs act on the body. Here, this study explored the ability of a slow-releasing injectable hydrogel depot to reduce dose-limiting toxicities of immunostimulatory CD40agonist (CD40a) while maintaining its potent anticancer efficacy. A previously described polymer-nanoparticle (PNP) hydrogel system is leveraged that exhibits shear-thinning and yield-stress properties that are hypothesized to improve locoregional delivery of CD40a immunotherapy. Using positron emission tomography, it is demonstrated that prolonged hydrogel-based delivery redistributes CD40a exposure to the tumor and the tumor draining lymph node (TdLN), thereby reducing weight loss, hepatotoxicity, and cytokine storm associated with standard treatment. Moreover, CD40a-loaded hydrogels mediate improved local cytokine induction in the TdLN and improve treatment efficacy in the B16F10melanoma model. PNP hydrogels, therefore, represent a facile, drug-agnostic method to ameliorate immune-related adverse effects and explore locoregional delivery of immunostimulatory drugs.

  View details for DOI 10.1002/advs.202103677

  View details for PubMedID 35975424

• Hydrogel-Based Slow Release of a Receptor-Binding Domain Subunit Vaccine Elicits Neutralizing Antibody Responses Against SARS-CoV-2. Advanced materials (Deerfield Beach, Fla.) Gale, E. C., Powell, A. E., Roth, G. A., Meany, E. L., Yan, J., Ou, B. S., Grosskopf, A. K., Adamska, J., Picece, V. C., d'Aquino, A. I., Pulendran, B., Kim, P. S., Appel, E. A. 2021: e2104362

  Abstract

  The development of effective vaccines that can be rapidly manufactured and distributed worldwide is necessary to mitigate the devastating health and economic impacts of pandemics like COVID-19. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, which mediates host cell entry of the virus, is an appealing antigen for subunit vaccines because it is efficient to manufacture, highly stable, and a target for neutralizing antibodies. Unfortunately, RBD is poorly immunogenic. While most subunit vaccines are commonly formulated with adjuvants to enhance their immunogenicity, clinically-relevant adjuvants Alum, AddaVax, and CpG/Alum are found unable to elicit neutralizing responses following a prime-boost immunization. Here, it has been shown that sustained delivery of an RBD subunit vaccine comprisingCpG/Alumadjuvant in an injectable polymer-nanoparticle (PNP) hydrogelelicited potentanti-RBD andanti-spikeantibody titers, providing broader protection against SARS-CoV-2 variants of concern compared to bolus administration of the same vaccine and vaccines comprising other clinically-relevant adjuvant systems. Notably, a SARS-CoV-2 spike-pseudotyped lentivirus neutralization assay revealed that hydrogel-based vaccines elicited potent neutralizing responses when bolus vaccines didnot. Together, these results suggest that slow delivery of RBD subunit vaccines with PNP hydrogels can significantly enhance the immunogenicity of RBD and induce neutralizing humoral immunity.

  View details for DOI 10.1002/adma.202104362

  View details for PubMedID 34651342