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27 results on '"Brocato, Rebecca L"'

3. Safety and Immunogenicity of an Andes Virus DNA Vaccine by Needle-Free Injection: A Randomized, Controlled Phase 1 Study.

Author

Paulsen, Grant C, Frenck, Robert, Tomashek, Kay M, Alarcon, Rodolfo M, Hensel, Elizabeth, Lowe, Ashley, Brocato, Rebecca L, Kwilas, Steve A, Josleyn, Matthew D, and Hooper, Jay W

Subjects
DNA vaccines, SEROCONVERSION, DNA viruses, VIRAL vaccines, IMMUNE response, CLINICAL trial registries
Abstract

Background Andes virus (ANDV), a rodent-borne hantavirus, causes hantavirus pulmonary syndrome (HPS). The safety and immunogenicity of a novel ANDV DNA vaccine was evaluated. Methods Phase 1, double-blind, dose-escalation trial randomly assigned 48 healthy adults to placebo or ANDV DNA vaccine delivered via needle-free jet injection. Cohorts 1 and 2 received 2 mg of DNA or placebo in a 3-dose (days 1, 29, 169) or 4-dose (days 1, 29, 57, 169) schedule, respectively. Cohorts 3 and 4 received 4 mg of DNA or placebo in the 3-dose and 4-dose schedule, respectively. Subjects were monitored for safety and neutralizing antibodies by pseudovirion neutralization assay (PsVNA50) and plaque reduction neutralization test (PRNT50). Results While 98% and 65% of subjects had at least 1 local or systemic solicited adverse event (AE), respectively, most AEs were mild or moderate; no related serious AEs were detected. Cohorts 2, 3, and 4 had higher seroconversion rates than cohort 1 and seropositivity of at least 80% by day 197, sustained through day 337. PsVNA50 geometric mean titers were highest for cohort 4 on and after day 197. Conclusions This first-in-human candidate HPS vaccine trial demonstrated that an ANDV DNA vaccine was safe and induced a robust, durable immune response. Clinical Trials Registration. NCT03682107. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Antigenic mapping and functional characterization of human New World hantavirus neutralizing antibodies

Author

Engdahl, Taylor B, primary, Binshtein, Elad, primary, Brocato, Rebecca L, primary, Kuzmina, Natalia A, additional, Principe, Lucia M, additional, Kwilas, Steven A, additional, Kim, Robert K, additional, Chapman, Nathaniel S, additional, Porter, Monique S, additional, Guardado-Calvo, Pablo, additional, Rey, Félix A, additional, Handal, Laura S, additional, Diaz, Summer M, additional, Zagol-Ikapitte, Irene A, additional, Tran, Minh H, additional, McDonald, W Hayes, additional, Meiler, Jens, additional, Reidy, Joseph X, additional, Trivette, Andrew, additional, Bukreyev, Alexander, additional, Hooper, Jay W, additional, and Crowe, James E, additional

Published
2023
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5. Author response: Antigenic mapping and functional characterization of human New World hantavirus neutralizing antibodies

Author

Engdahl, Taylor B, primary, Binshtein, Elad, primary, Brocato, Rebecca L, primary, Kuzmina, Natalia A, additional, Principe, Lucia M, additional, Kwilas, Steven A, additional, Kim, Robert K, additional, Chapman, Nathaniel S, additional, Porter, Monique S, additional, Guardado-Calvo, Pablo, additional, Rey, Félix A, additional, Handal, Laura S, additional, Diaz, Summer M, additional, Zagol-Ikapitte, Irene A, additional, Tran, Minh H, additional, McDonald, W Hayes, additional, Meiler, Jens, additional, Reidy, Joseph X, additional, Trivette, Andrew, additional, Bukreyev, Alexander, additional, Hooper, Jay W, additional, and Crowe, James E, additional

Published
2023
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6. Antigenic mapping and functional characterization of human New World hantavirus neutralizing antibodies

Author

Engdahl, Taylor B., primary, Binshtein, Elad, additional, Brocato, Rebecca L., additional, Kuzmina, Natalia A., additional, Principe, Lucia M, additional, Kwilas, Steven A., additional, Kim, Robert K., additional, Chapman, Nathaniel S., additional, Porter, Monique S., additional, Guardado-Calvo, Pablo, additional, Rey, Felix A., additional, Handal, Laura S., additional, Diaz, Summer M., additional, Zagol-Ikapitte, Irene A., additional, Reidy, Joseph X., additional, Trivette, Andrew, additional, Bukreyev, Alexander, additional, Hooper, Jay W., additional, and Crowe, James. E., additional

Published
2022
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12. Disruption of Adaptive Immunity Enhances Disease in SARS-CoV-2-Infected Syrian Hamsters

Author

Brocato, Rebecca L., primary, Principe, Lucia M., additional, Kim, Robert K., additional, Zeng, Xiankun, additional, Williams, Janice A., additional, Liu, Yanan, additional, Li, Rong, additional, Smith, Jeffrey M., additional, Golden, Joseph W., additional, Gangemi, Dave, additional, Youssef, Sawsan, additional, Wang, Zhongde, additional, Glanville, Jacob, additional, and Hooper, Jay W., additional

Published
2020
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13. Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease

Author

Golden, Joseph W., primary, Cline, Curtis R., additional, Zeng, Xiankun, additional, Garrison, Aura R., additional, Carey, Brian D., additional, Mucker, Eric M., additional, White, Lauren E., additional, Shamblin, Joshua D., additional, Brocato, Rebecca L., additional, Liu, Jun, additional, Babka, April M., additional, Rauch, Hypaitia B., additional, Smith, Jeffrey M., additional, Hollidge, Bradley S., additional, Fitzpatrick, Collin, additional, Badger, Catherine V., additional, and Hooper, Jay W., additional

Published
2020
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14. Anti-HFRS Human IgG Produced in Transchromosomic Bovines Has Potent Hantavirus Neutralizing Activity and Is Protective in Animal Models

Author

Perley, Casey C., primary, Brocato, Rebecca L., additional, Wu, Hua, additional, Bausch, Christoph, additional, Karmali, Priya P., additional, Vega, Jerel B., additional, Cohen, Melanie V., additional, Somerville, Brandon, additional, Kwilas, Steven A., additional, Principe, Lucia M., additional, Shamblin, Joshua, additional, Chivukula, Padmanabh, additional, Sullivan, Eddie, additional, and Hooper, Jay W., additional

Published
2020
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17. Pichinde virus induces microvascular endothelial cell permeability through the production of nitric oxide

Author

Voss Thomas G and Brocato Rebecca L

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Abstract This report is the first to demonstrate infection of human endothelial cells by Pichinde virus (PIC). PIC infection induces an upregulation of the inducible nitric oxide synthase gene; as well as an increase in detectable nitric oxide (NO). PIC induces an increase in permeability in endothelial cell monolayers which can be abrogated at all measured timepoints with the addition of a nitric oxide synthase inhibitor, indicating a role for NO in the alteration of endothelial barrier function. Because NO has shown antiviral activity against some viruses, viral titer was measured after addition of the NO synthase inhibitor and found to have no effect in altering virus load in infected EC. The NO synthase inhibition also has no effect on levels of activated caspases induced by PIC infection. Taken together, these data indicate NO production induced by Pichinde virus infection has a pathogenic effect on endothelial cell monolayer permeability.

Published
2009
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20. Animal Models for the Study of Rodent-Borne Hemorrhagic Fever Viruses: Arenaviruses and Hantaviruses

Author

Golden, Joseph W., Hammerbeck, Christopher D., Mucker, Eric M., and Brocato, Rebecca L.

Subjects
Article Subject, viruses, virus diseases
Abstract

Human pathogenic hantaviruses and arenaviruses are maintained in nature by persistent infection of rodent carrier populations. Several members of these virus groups can cause significant disease in humans that is generically termed viral hemorrhagic fever (HF) and is characterized as a febrile illness with an increased propensity to cause acute inflammation. Human interaction with rodent carrier populations leads to infection. Arenaviruses are also viewed as potential biological weapons threat agents. There is an increased interest in studying these viruses in animal models to gain a deeper understating not only of viral pathogenesis, but also for the evaluation of medical countermeasures (MCM) to mitigate disease threats. In this review, we examine current knowledge regarding animal models employed in the study of these viruses. We include analysis of infection models in natural reservoirs and also discuss the impact of strain heterogeneity on the susceptibility of animals to infection. This information should provide a comprehensive reference for those interested in the study of arenaviruses and hantaviruses not only for MCM development but also in the study of viral pathogenesis and the biology of these viruses in their natural reservoirs.

Published
2015
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22. Antiviral Biologic Produced in DNA Vaccine/Goose Platform Protects Hamsters Against Hantavirus Pulmonary Syndrome When Administered Post-exposure

Author

Haese, Nicole, primary, Brocato, Rebecca L., additional, Henderson, Thomas, additional, Nilles, Matthew L., additional, Kwilas, Steve A., additional, Josleyn, Matthew D., additional, Hammerbeck, Christopher D., additional, Schiltz, James, additional, Royals, Michael, additional, Ballantyne, John, additional, Hooper, Jay W., additional, and Bradley, David S., additional

Published
2015
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24. DNA vaccine–derived human IgG produced in transchromosomal bovines protect in lethal models of hantavirus pulmonary syndrome

Author

Hooper, Jay W., primary, Brocato, Rebecca L., additional, Kwilas, Steven A., additional, Hammerbeck, Christopher D., additional, Josleyn, Matthew D., additional, Royals, Michael, additional, Ballantyne, John, additional, Wu, Hua, additional, Jiao, Jin-an, additional, Matsushita, Hiroaki, additional, and Sullivan, Eddie J., additional

Published
2014
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27. Preclinical evaluation of a fully human, quadrivalent-hantavirus polyclonal antibody derived from a non-human source.

Author

Brocato RL, Wu H, Kwilas SA, Principe LM, Josleyn M, Shamblin J, Chivukula P, Bausch C, Luke T, Sullivan EJ, and Hooper JW

Subjects
Animals, Humans, Cattle, Mesocricetus, Drug Evaluation, Preclinical, Cricetinae, Female, Antibodies, Viral immunology, Antibodies, Neutralizing immunology, Orthohantavirus immunology, Orthohantavirus genetics, Hantavirus Infections immunology, Hantavirus Infections prevention & control, Hantavirus Infections virology
Abstract

Hantaviruses are rodent-borne viruses that cause severe disease in infected humans. In the New World, major hantaviruses include Andes virus (ANDV) and Sin Nombre virus (SNV) causing hantavirus pulmonary syndrome. In the Old World, major hantaviruses include Hantaan virus (HTNV) and Puumala virus (PUUV) causing hemorrhagic fever with renal syndrome. Here, we produced a pan-hantavirus therapeutic (SAB-163) comprised of fully human immunoglobulin purified from the plasma of transchromosomic bovines (TcB) vaccinated with hantavirus DNA plasmids coding for the major glycoproteins of ANDV, SNV, HTNV, and PUUV. SAB-163 has potent neutralizing antibodies (PRNT50 > 200,000) against the four targeted hantavirus and cross-neutralization against several other heterotypic hantaviruses. At a dosage of 10 mg/kg, SAB-163 is bioavailable in Syrian hamsters out to 70 days post-treatment with a half-life of 10-15 days. At this same dosage, SAB-163 administered 1 day before, or 5 days after exposure, protected all hamsters from lethal disease caused by ANDV. At a higher dose, partial but significant protection was achieved as late as day 6. SAB-163 also protected hamsters in the HTNV, PUUV, and SNV infection models when administered 1 day before or up to 3 days after challenge. This pan-hantavirus therapeutic is attractive because it is fully human, multi-targeted, safe, stable at 4°C, and effective in animal models. SAB-163 was evaluated for safety in GLP human tissue binding studies and a GLP rabbit toxicity study at 365 and 730 mg/kg and is investigational new drug enabled for phase 1 clinical trial(s)., Importance: This candidate polyclonal human IgG product was produced using synthetic gene-based vaccines and transgenic cows. Having now gone through cGMP production, GLP safety testing, and efficacy testing in animals, SAB-163 is the world's most advanced anti-hantavirus antibody-based medical countermeasure, aside from convalescent human plasma. Importantly, SAB-163 targets the most prevalent hantaviruses on four continents., Competing Interests: P.C., E.J.S., and J.W.H. are inventors on patents or patents pending related to technology used to develop proof-of-concept antibody-based products described in the paper (i.e., lipid nanoparticles, Tc bovine, and DNA vaccines).

Published
2024
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