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1. Broad and potently neutralizing monoclonal antibodies isolated from human survivors of New World hantavirus infection

Author

Taylor B. Engdahl, Natalia A. Kuzmina, Adam J. Ronk, Chad E. Mire, Matthew A. Hyde, Nurgun Kose, Matthew D. Josleyn, Rachel E. Sutton, Apoorva Mehta, Rachael M. Wolters, Nicole M. Lloyd, Francisca R. Valdivieso, Thomas G. Ksiazek, Jay W. Hooper, Alexander Bukreyev, and James E. Crowe, Jr.

Subjects
hantavirus, Bunyavirus, cross-reactivity, Sin Nombre virus, Andes virus, infection, Biology (General), QH301-705.5
Abstract

Summary: New World hantaviruses (NWHs) are endemic in North and South America and cause hantavirus cardiopulmonary syndrome (HCPS), with a case fatality rate of up to 40%. Knowledge of the natural humoral immune response to NWH infection is limited. Here, we describe human monoclonal antibodies (mAbs) isolated from individuals previously infected with Sin Nombre virus (SNV) or Andes virus (ANDV). Most SNV-reactive antibodies show broad recognition and cross-neutralization of both New and Old World hantaviruses, while many ANDV-reactive antibodies show activity for ANDV only. mAbs ANDV-44 and SNV-53 compete for binding to a distinct site on the ANDV surface glycoprotein and show potently neutralizing activity to New and Old World hantaviruses. Four mAbs show therapeutic efficacy at clinically relevant doses in hamsters. These studies reveal a convergent and potently neutralizing human antibody response to NWHs and suggest therapeutic potential for human mAbs against HCPS.

Published
2021
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2. Nanoceria: Metabolic interactions and delivery through PLGA-encapsulation

Author

Apoorva Mehta, Mikhail Bredikhin, T. O. Shekunova, Dmitry Gil, Bradley Scammon, Kevin Shrake, Vladimir Ivanov, Vladimir Reukov, and Alexander E. Baranchikov

Subjects
Materials science, Biocompatibility, Bioengineering, 02 engineering and technology, 010402 general chemistry, medicine.disease_cause, 01 natural sciences, Antioxidants, Biomaterials, Superoxide dismutase, chemistry.chemical_compound, medicine, Cytotoxicity, chemistry.chemical_classification, Reactive oxygen species, biology, Superoxide Dismutase, Cerium, Hydrogen Peroxide, Catalase, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Oxidative Stress, PLGA, chemistry, Mechanics of Materials, Biophysics, biology.protein, Nanoparticles, Lysozyme, Reactive Oxygen Species, 0210 nano-technology, Oxidative stress
Abstract

Cerium oxide nanoparticles (nanoceria) have recyclable antioxidative activity. It has numerous potential applications in biomedical engineering, such as mitigating damage from burns, radiation, and bacterial infection. This mitigating activity is analogous to that property of metabolic enzymes such as superoxide dismutase (SOD) and catalase - scavengers of reactive oxygen species (ROS). Therefore, nanoceria can protect cells from environmental oxidative stress. This therapeutic effect prompted studies of nanoceria and metabolic enzymes as a combination therapy. The activity and structure of SOD, catalase, and lysozyme were examined in the presence of nanoceria. A complementary relationship between SOD and nanoceria motivated the present work, in which we explored a method for simultaneous delivery of SOD and nanoceria. The biocompatibility and tunable degradation of poly(lactic-co-glycolic acid) (PLGA) made it a candidate material for encapsulating both nanoceria and SOD. Cellular uptake studies were conducted along with a cytotoxicity assay. The antioxidative properties of PLGA-nanoceria-SOD particles were verified by adding H2O2 to cell culture and imaging with fluorescent markers of oxidative stress. Our results suggest that PLGA is a suitable encapsulating carrier for simultaneous delivering nanoceria and SOD together, and that this combination effectively reduces oxidative stress in vitro.

Published
2020
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