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Biopharmaceutics 4.0, Advanced Pre-Clinical Development of mRNA-Encoded Monoclonal Antibodies to Immunosuppressed Murine Models

Administration of mRNA against SARS-CoV-2 has demonstrated sufficient efficacy, tolerability and clinical potential to disrupt the vaccination field. A multiple-arm, cohort randomized, mixed blind, placebo-controlled study was designed to investigate the in vivo expression of mRNA antibodies to immu...

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Autores principales: Ouranidis, Andreas, Choli-Papadopoulou, Theodora, Papachristou, Eleni T., Papi, Rigini, Kostomitsopoulos, Nikolaos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402437/
https://www.ncbi.nlm.nih.gov/pubmed/34452015
http://dx.doi.org/10.3390/vaccines9080890
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author Ouranidis, Andreas
Choli-Papadopoulou, Theodora
Papachristou, Eleni T.
Papi, Rigini
Kostomitsopoulos, Nikolaos
author_facet Ouranidis, Andreas
Choli-Papadopoulou, Theodora
Papachristou, Eleni T.
Papi, Rigini
Kostomitsopoulos, Nikolaos
author_sort Ouranidis, Andreas
collection PubMed
description Administration of mRNA against SARS-CoV-2 has demonstrated sufficient efficacy, tolerability and clinical potential to disrupt the vaccination field. A multiple-arm, cohort randomized, mixed blind, placebo-controlled study was designed to investigate the in vivo expression of mRNA antibodies to immunosuppressed murine models to conduct efficacy, safety and bioavailability evaluation. Enabling 4.0 tools we reduced animal sacrifice, while interventions were designed compliant to HARRP and SPIRIT engagement: (a) Randomization, blinding; (b) pharmaceutical grade formulation, monitoring; (c) biochemical and histological analysis; and (d) theoretic, statistical analysis. Risk assessment molded the study orientations, according to the ARRIVE guidelines. The primary target of this protocol is the validation of the research hypothesis that autologous translation of Trastuzumab by in vitro transcribed mRNA-encoded antibodies to immunosuppressed animal models, is non-inferior to classical treatments. The secondary target is the comparative pharmacokinetic assessment of the novel scheme, between immunodeficient and healthy subjects. Herein, the debut clinical protocol, investigating the pharmacokinetic/pharmacodynamic impact of mRNA vaccination to immunodeficient organisms. Our design, contributes novel methodology to guide the preclinical development of RNA antibody modalities by resolving efficacy, tolerability and dose regime adjustment for special populations that are incapable of humoral defense.
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spelling pubmed-84024372021-08-29 Biopharmaceutics 4.0, Advanced Pre-Clinical Development of mRNA-Encoded Monoclonal Antibodies to Immunosuppressed Murine Models Ouranidis, Andreas Choli-Papadopoulou, Theodora Papachristou, Eleni T. Papi, Rigini Kostomitsopoulos, Nikolaos Vaccines (Basel) Article Administration of mRNA against SARS-CoV-2 has demonstrated sufficient efficacy, tolerability and clinical potential to disrupt the vaccination field. A multiple-arm, cohort randomized, mixed blind, placebo-controlled study was designed to investigate the in vivo expression of mRNA antibodies to immunosuppressed murine models to conduct efficacy, safety and bioavailability evaluation. Enabling 4.0 tools we reduced animal sacrifice, while interventions were designed compliant to HARRP and SPIRIT engagement: (a) Randomization, blinding; (b) pharmaceutical grade formulation, monitoring; (c) biochemical and histological analysis; and (d) theoretic, statistical analysis. Risk assessment molded the study orientations, according to the ARRIVE guidelines. The primary target of this protocol is the validation of the research hypothesis that autologous translation of Trastuzumab by in vitro transcribed mRNA-encoded antibodies to immunosuppressed animal models, is non-inferior to classical treatments. The secondary target is the comparative pharmacokinetic assessment of the novel scheme, between immunodeficient and healthy subjects. Herein, the debut clinical protocol, investigating the pharmacokinetic/pharmacodynamic impact of mRNA vaccination to immunodeficient organisms. Our design, contributes novel methodology to guide the preclinical development of RNA antibody modalities by resolving efficacy, tolerability and dose regime adjustment for special populations that are incapable of humoral defense. MDPI 2021-08-11 /pmc/articles/PMC8402437/ /pubmed/34452015 http://dx.doi.org/10.3390/vaccines9080890 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ouranidis, Andreas
Choli-Papadopoulou, Theodora
Papachristou, Eleni T.
Papi, Rigini
Kostomitsopoulos, Nikolaos
Biopharmaceutics 4.0, Advanced Pre-Clinical Development of mRNA-Encoded Monoclonal Antibodies to Immunosuppressed Murine Models
title Biopharmaceutics 4.0, Advanced Pre-Clinical Development of mRNA-Encoded Monoclonal Antibodies to Immunosuppressed Murine Models
title_full Biopharmaceutics 4.0, Advanced Pre-Clinical Development of mRNA-Encoded Monoclonal Antibodies to Immunosuppressed Murine Models
title_fullStr Biopharmaceutics 4.0, Advanced Pre-Clinical Development of mRNA-Encoded Monoclonal Antibodies to Immunosuppressed Murine Models
title_full_unstemmed Biopharmaceutics 4.0, Advanced Pre-Clinical Development of mRNA-Encoded Monoclonal Antibodies to Immunosuppressed Murine Models
title_short Biopharmaceutics 4.0, Advanced Pre-Clinical Development of mRNA-Encoded Monoclonal Antibodies to Immunosuppressed Murine Models
title_sort biopharmaceutics 4.0, advanced pre-clinical development of mrna-encoded monoclonal antibodies to immunosuppressed murine models
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402437/
https://www.ncbi.nlm.nih.gov/pubmed/34452015
http://dx.doi.org/10.3390/vaccines9080890
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