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Your search keyword '"Michaela Helble"' showing total 3 results
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3 results on '"Michaela Helble"'

1. Engineered antibody cytokine chimera synergizes with DNA-launched nanoparticle vaccines to potentiate melanoma suppression in vivo

Author

Nicholas J. Tursi, Ziyang Xu, Michaela Helble, Susanne Walker, Kevin Liaw, Neethu Chokkalingam, Toshitha Kannan, Yuanhan Wu, Edgar Tello-Ruiz, Daniel H. Park, Xizhou Zhu, Megan C. Wise, Trevor R. F. Smith, Sonali Majumdar, Andrew Kossenkov, Daniel W. Kulp, and David B. Weiner

Subjects
cancer immunotherapy, antibody cytokine chimera, DNA vaccines, nanoparticle vaccines, melanoma, Immunologic diseases. Allergy, RC581-607
Abstract

Cancer immunotherapy has demonstrated great promise with several checkpoint inhibitors being approved as the first-line therapy for some types of cancer, and new engineered cytokines such as Neo2/15 now being evaluated in many studies. In this work, we designed antibody-cytokine chimera (ACC) scaffolding cytokine mimetics on a full-length tumor-specific antibody. We characterized the pharmacokinetic (PK) and pharmacodynamic (PD) properties of first-generation ACC TA99-Neo2/15, which synergized with DLnano-vaccines to suppress in vivo melanoma proliferation and induced significant systemic cytokine activation. A novel second-generation ACC TA99-HL2-KOA1, with retained IL-2Rβ/γ binding and attenuated but preserved IL-2Rα binding, induced lower systemic cytokine activation with non-inferior protection in murine tumor studies. Transcriptomic analyses demonstrated an upregulation of Type I interferon responsive genes, particularly ISG15, in dendritic cells, macrophages and monocytes following TA99-HL2-KOA1 treatment. Characterization of additional ACCs in combination with cancer vaccines will likely be an important area of research for treating melanoma and other types of cancer.

Published
2023
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2. SARS-CoV-2 Assays To Detect Functional Antibody Responses That Block ACE2 Recognition in Vaccinated Animals and Infected Patients

Author

Kate E. Broderick, David B. Weiner, Pablo Tebas, Emma L. Reuschel, Mansi Purwar, Katherine Schultheis, Daniel W. Kulp, Karuppiah Muthumani, Neethu Chokkalingam, Ami Patel, Trevor R.F. Smith, Susanne Walker, Stephanie Ramos, Kevin Kim, Ebony N. Gary, Michaela Helble, Ziyang Xu, and Jewell Walters

Subjects
Primates, serological tests, Microbiology (medical), COVID-19 Vaccines, Guinea Pigs, Pneumonia, Viral, Enzyme-Linked Immunosorbent Assay, Peptidyl-Dipeptidase A, medicine.disease_cause, Antibodies, Viral, Immunoglobulin G, Neutralization, Serology, ACE2 blocking assay, Betacoronavirus, Mice, COVID-19 Testing, Neutralization Tests, SARS-CoV-2 vaccine, medicine, Animals, Humans, Antibodies, Blocking, Immunoassays, Pandemics, Coronavirus, biology, business.industry, Clinical Laboratory Techniques, SARS-CoV-2, Viral Vaccine, SARS-CoV-2 immunity, fungi, functional antibodies, COVID-19, Viral Vaccines, Surface Plasmon Resonance, Vaccine efficacy, Virology, Antibodies, Neutralizing, Titer, Spike Glycoprotein, Coronavirus, biology.protein, Angiotensin-Converting Enzyme 2, Rabbits, Antibody, business, Coronavirus Infections
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of COVID-19, resulting in cases of mild to severe respiratory distress and significant mortality. The global outbreak of this novel coronavirus has now infected >20 million people worldwide, with >5 million cases in the United States (11 August 2020). The development of diagnostic and research tools to determine infection and vaccine efficacy is critically needed., Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of COVID-19, resulting in cases of mild to severe respiratory distress and significant mortality. The global outbreak of this novel coronavirus has now infected >20 million people worldwide, with >5 million cases in the United States (11 August 2020). The development of diagnostic and research tools to determine infection and vaccine efficacy is critically needed. We have developed multiple serologic assays using newly designed SARS-CoV-2 reagents for detecting the presence of receptor-binding antibodies in sera. The first assay is surface plasmon resonance (SPR) based and can quantitate both antibody binding to the SARS-CoV-2 spike protein and blocking to the Angiotensin-converting enzyme 2 (ACE2) receptor in a single experiment. The second assay is enzyme-linked immunosorbent assay (ELISA) based and can measure competition and blocking of the ACE2 receptor to the SARS-CoV-2 spike protein with antispike antibodies. The assay is highly versatile, and we demonstrate the broad utility of the assay by measuring antibody functionality of sera from small animals and nonhuman primates immunized with an experimental SARS-CoV-2 vaccine. In addition, we employ the assay to measure receptor blocking of sera from SARS-CoV-2-infected patients. The assay is shown to correlate with pseudovirus neutralization titers. This type of rapid, surrogate neutralization diagnostic can be employed widely to help study SARS-CoV-2 infection and assess the efficacy of vaccines.

Published
2020
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