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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doaj-6bf4dc3a823b4905b1e8c0e0e96a1d162021-08-26T14:25:52ZengMDPI AGVaccines2076-393X2021-08-01989089010.3390/vaccines9080890Biopharmaceutics 4.0, Advanced Pre-Clinical Development of mRNA-Encoded Monoclonal Antibodies to Immunosuppressed Murine ModelsAndreas Ouranidis0Theodora Choli-Papadopoulou1Eleni T. Papachristou2Rigini Papi3Nikolaos Kostomitsopoulos4Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceDepartment of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceDepartment of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceDepartment of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceCenter of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, GreeceAdministration 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.https://www.mdpi.com/2076-393X/9/8/890mRNA encoded antibodiesSARS–CoV-2COVID-19TrastuzumabmRNA-vaccinespharmacokinetics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Andreas Ouranidis Theodora Choli-Papadopoulou Eleni T. Papachristou Rigini Papi Nikolaos Kostomitsopoulos |
spellingShingle |
Andreas Ouranidis Theodora Choli-Papadopoulou Eleni T. Papachristou Rigini Papi Nikolaos Kostomitsopoulos Biopharmaceutics 4.0, Advanced Pre-Clinical Development of mRNA-Encoded Monoclonal Antibodies to Immunosuppressed Murine Models Vaccines mRNA encoded antibodies SARS–CoV-2 COVID-19 Trastuzumab mRNA-vaccines pharmacokinetics |
author_facet |
Andreas Ouranidis Theodora Choli-Papadopoulou Eleni T. Papachristou Rigini Papi Nikolaos Kostomitsopoulos |
author_sort |
Andreas Ouranidis |
title |
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_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_sort |
biopharmaceutics 4.0, advanced pre-clinical development of mrna-encoded monoclonal antibodies to immunosuppressed murine models |
publisher |
MDPI AG |
series |
Vaccines |
issn |
2076-393X |
publishDate |
2021-08-01 |
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. |
topic |
mRNA encoded antibodies SARS–CoV-2 COVID-19 Trastuzumab mRNA-vaccines pharmacokinetics |
url |
https://www.mdpi.com/2076-393X/9/8/890 |
work_keys_str_mv |
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