PMID- 36681171 OWN - NLM STAT- MEDLINE DCOM- 20230420 LR - 20230421 IS - 1549-9642 (Electronic) IS - 1549-9634 (Linking) VI - 49 DP - 2023 Apr TI - Coatsome-replicon vehicles: Self-replicating RNA vaccines against infectious diseases. PG - 102655 LID - S1549-9634(23)00006-0 [pii] LID - 10.1016/j.nano.2023.102655 [doi] AB - Herein, we provide the first description of a synthetic delivery method for self-replicating replicon RNAs (RepRNA) derived from classical swine fever virus (CSFV) using a Coatsome-replicon vehicle based on Coatsome(R) SS technologies. This results in an unprecedented efficacy when compared to well-established polyplexes, with up to approximately 65 fold-increase of the synthesis of RepRNA-encoded gene of interest (GOI). We demonstrated the efficacy of such Coatsome-replicon vehicles for RepRNA-mediated induction of CD8 T-cell responses in mice. Moreover, we provide new insights on physical properties of the RepRNA, showing that the removal of all CSFV structural protein genes has a positive effect on the translation of the GOI. Finally, we successfully engineered RepRNA constructs encoding a porcine reproductive and respiratory syndrome virus (PRRSV) antigen, providing an example of antigen expression with potential application to combat viral diseases. The versatility and simplicity of modifying and manufacturing these Coatsome-replicon vehicle formulations represents a major asset to tackle foreseeable emerging pandemics. CI - Copyright (c) 2023 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Demoulins, Thomas AU - Demoulins T AD - Institute of Virology and Immunology IVI, Bern & Mittelhausern, Switzerland; Institute of Veterinary Bacteriology, University of Bern, Bern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland; Department of Veterinary Microbiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand; Center of Excellence in Emerging Infectious Diseases in Animals, Chulalongkorn University (CU-EIDAs), Bangkok, Thailand. Electronic address: thomas.demoulins@unibe.ch. FAU - Schulze, Kai AU - Schulze K AD - Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany. FAU - Ebensen, Thomas AU - Ebensen T AD - Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany. FAU - Techakriengkrai, Navapon AU - Techakriengkrai N AD - Department of Veterinary Microbiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand; Center of Excellence in Emerging Infectious Diseases in Animals, Chulalongkorn University (CU-EIDAs), Bangkok, Thailand. FAU - Nedumpun, Teerawut AU - Nedumpun T AD - Department of Veterinary Microbiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand; Center of Excellence in Emerging Infectious Diseases in Animals, Chulalongkorn University (CU-EIDAs), Bangkok, Thailand. FAU - Englezou, Pavlos C AU - Englezou PC AD - Institute of Virology and Immunology IVI, Bern & Mittelhausern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland. FAU - Gerber, Markus AU - Gerber M AD - Institute of Virology and Immunology IVI, Bern & Mittelhausern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland. FAU - Hlushchuk, Ruslan AU - Hlushchuk R AD - Institute of Anatomy, University of Bern, Bern, Switzerland. FAU - Toledo, Darien AU - Toledo D AD - Institute of Pharmacology, University of Bern, Bern, Switzerland. FAU - Djonov, Valentin AU - Djonov V AD - Institute of Anatomy, University of Bern, Bern, Switzerland. FAU - von Gunten, Stephan AU - von Gunten S AD - Institute of Pharmacology, University of Bern, Bern, Switzerland. FAU - McCullough, Kenneth C AU - McCullough KC AD - Institute of Virology and Immunology IVI, Bern & Mittelhausern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland. FAU - Liniger, Matthias AU - Liniger M AD - Institute of Virology and Immunology IVI, Bern & Mittelhausern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland. FAU - Guzman, Carlos A AU - Guzman CA AD - Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany. FAU - Suradhat, Sanipa AU - Suradhat S AD - Department of Veterinary Microbiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand; Center of Excellence in Emerging Infectious Diseases in Animals, Chulalongkorn University (CU-EIDAs), Bangkok, Thailand. FAU - Ruggli, Nicolas AU - Ruggli N AD - Institute of Virology and Immunology IVI, Bern & Mittelhausern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230118 PL - United States TA - Nanomedicine JT - Nanomedicine : nanotechnology, biology, and medicine JID - 101233142 RN - 63231-63-0 (RNA) RN - 0 (Antigens) SB - IM MH - Swine MH - Mice MH - Animals MH - *RNA/genetics MH - Antigens MH - *Communicable Diseases/genetics MH - Replicon/genetics OTO - NOTNLM OT - Coatsome-replicon vehicle OT - Porcine reproductive and respiratory syndrome virus (PRRSV) OT - Self-amplifying replicon RNA (RepRNA) OT - Structural protein genes OT - c-di-AMP COIS- Declaration of competing interest A patent for the application of delivery vehicles for the delivery of RepRNA vaccines to DCs using replicons derived from classical swine fever virus, as employed in this paper, has been filed in Europe and granted in USA, Canada, and India, with priority date of 4 June 2008. The filing was by Kenneth C. McCullough, Nicolas Ruggli and Jon Duri Tratschin (all three as inventors) (WO 2009146867), and assigned to their employer - the Institute of Virology and Immunology IVI. This does not alter the authors' adherence to the policies of sharing data and materials. Carlos A. Guzman and Thomas Ebensen are named as inventors in a patent application covering the use of c-di-AMP as adjuvant (PCT/EP 2006010693). EDAT- 2023/01/22 06:00 MHDA- 2023/04/20 10:17 CRDT- 2023/01/21 19:25 PHST- 2022/10/10 00:00 [received] PHST- 2022/12/20 00:00 [revised] PHST- 2023/01/05 00:00 [accepted] PHST- 2023/04/20 10:17 [medline] PHST- 2023/01/22 06:00 [pubmed] PHST- 2023/01/21 19:25 [entrez] AID - S1549-9634(23)00006-0 [pii] AID - 10.1016/j.nano.2023.102655 [doi] PST - ppublish SO - Nanomedicine. 2023 Apr;49:102655. doi: 10.1016/j.nano.2023.102655. Epub 2023 Jan 18.