title: Additives for vaccine storage to improve thermal stability of adenoviruses from hours to months.
abstract: Up to 80% of the cost of vaccination programmes is due to the cold chain problem (that is, keeping vaccines cold). Inexpensive, biocompatible additives to slow down the degradation of virus particles would address the problem. Here we propose and characterize additives that, already at very low concentrations, improve the storage time of adenovirus type 5. Anionic gold nanoparticles (10-8-10-6M) or polyethylene glycol (PEG, molecular weight ∼8,000 Da, 10-7-10-4M) increase the half-life of a green fluorescent protein expressing adenovirus from ∼48 h to 21 days at 37 °C (from 7 to >30 days at room temperature). They replicate the known stabilizing effect of sucrose, but at several orders of magnitude lower concentrations. PEG and sucrose maintained immunogenicity in vivo for viruses stored for 10 days at 37 °C. To achieve rational design of viral-vaccine stabilizers, our approach is aided by simplified quantitative models based on a single rate-limiting step.
authors.affiliation: European School of Molecular Medicine (SEMM), IFOM-IEO-Campus, via Adamello 16, Milan 20139, Italy.|Università degli Studi di Milano, Milan 20122, Italy.|Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta, IFOM-IEO-campus, via Adamello 16, Milan 20139, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Pelliccia
authors.affiliation: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta, IFOM-IEO-campus, via Adamello 16, Milan 20139, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Andreozzi
authors.affiliation: Instituut-Lorentz for theoretical physics, Leiden University, 271, Niels Bohrweg 2, NL 2333 CA Leiden, The Netherlands.
authors.forename: Jayson
authors.initials: J
authors.lastname: Paulose
authors.affiliation: European School of Molecular Medicine (SEMM), IFOM-IEO-Campus, via Adamello 16, Milan 20139, Italy.|Università degli Studi di Milano, Milan 20122, Italy.|Fondazione CEN-European Centre for Nanomedicine, Piazza Leonardo da Vinci, 32, 20133 Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: D'Alicarnasso
authors.affiliation: Laboratory of Molecular Virology and Antiviral Research, Department of Clinical and Biological Sciences, University of Turin, S. Luigi Gonzaga Hospital, Regione Gonzole 10, 10043 Orbassano, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Cagno
authors.affiliation: Laboratory of Molecular Virology and Antiviral Research, Department of Clinical and Biological Sciences, University of Turin, S. Luigi Gonzaga Hospital, Regione Gonzole 10, 10043 Orbassano, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Donalisio
authors.affiliation: Laboratory of Molecular Virology and Antiviral Research, Department of Clinical and Biological Sciences, University of Turin, S. Luigi Gonzaga Hospital, Regione Gonzole 10, 10043 Orbassano, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Civra
authors.affiliation: Vaccine &Gene Therapy Institute, Oregon Health &Science University, 505 NW 185th Avenue, Beaverton, Oregon 97006, USA.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Broeckel
authors.affiliation: Vaccine &Gene Therapy Institute, Oregon Health &Science University, 505 NW 185th Avenue, Beaverton, Oregon 97006, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Haese
authors.affiliation: Institute of Materials and Interfaculty Bioengineering Institute, École polytechnique fédérale de Lausanne, STI IMX SUNMIL MXG 030, Station 12, CH-1015 Lausanne, Switzerland.
authors.forename: Paulo
authors.initials: P
authors.lastname: Jacob Silva
authors.affiliation: Institute of Materials and Interfaculty Bioengineering Institute, École polytechnique fédérale de Lausanne, STI IMX SUNMIL MXG 030, Station 12, CH-1015 Lausanne, Switzerland.
authors.forename: Randy P
authors.identifier: http://orcid.org/0000-0001-8193-1664
authors.initials: RP
authors.lastname: Carney
authors.affiliation: Department of Biological and Environmental Science/Nanoscience Center, University of Jyväskyla, Survontie 9, 40500 Jyväskyla, Finland.
authors.forename: Varpu
authors.initials: V
authors.lastname: Marjomäki
authors.affiliation: Vaccine &Gene Therapy Institute, Oregon Health &Science University, 505 NW 185th Avenue, Beaverton, Oregon 97006, USA.
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Streblow
authors.affiliation: Laboratory of Molecular Virology and Antiviral Research, Department of Clinical and Biological Sciences, University of Turin, S. Luigi Gonzaga Hospital, Regione Gonzole 10, 10043 Orbassano, Italy.
authors.forename: David
authors.initials: D
authors.lastname: Lembo
authors.affiliation: Institute of Materials and Interfaculty Bioengineering Institute, École polytechnique fédérale de Lausanne, STI IMX SUNMIL MXG 030, Station 12, CH-1015 Lausanne, Switzerland.
authors.forename: Francesco
authors.identifier: http://orcid.org/0000-0003-4635-6080
authors.initials: F
authors.lastname: Stellacci
authors.affiliation: Instituut-Lorentz for theoretical physics, Leiden University, 271, Niels Bohrweg 2, NL 2333 CA Leiden, The Netherlands.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Vitelli
authors.affiliation: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta, IFOM-IEO-campus, via Adamello 16, Milan 20139, Italy.|Laboratory of Translational Nanotechnology, I.R.C.C.S. Istituto Tumori Giovanni Paolo II, viale Orazio, Flacco 65, Bari 70124, Italy.
authors.forename: Silke
authors.initials: S
authors.lastname: Krol
mesh_terms: D062705:Adenovirus Vaccines / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D000818:Animals; D003080:Cold Temperature; D004355:Drug Stability; D004356:Drug Storage / Q000379:methods; D005079:Excipients / Q000737:chemistry*; D005240:Feasibility Studies; D006046:Gold / Q000737:chemistry; D006207:Half-Life; D000071497:Immunogenicity, Vaccine; D053768:Metal Nanoparticles / Q000737:chemistry; D051379:Mice; D023421:Models, Animal; D008954:Models, Biological; D011092:Polyethylene Glycols / Q000737:chemistry; D013395:Sucrose / Q000737:chemistry; D013997:Time Factors
chemical_list: D062705:Adenovirus Vaccines; D005079:Excipients; D011092:Polyethylene Glycols; D013395:Sucrose; D006046:Gold