Additives for vaccine storage to improve thermal stability of adenoviruses from hours to months

Maria Pelliccia, Patrizia Andreozzi, Jayson Paulose, Marco D’Alicarnasso, Valeria Cagno, Manuela Donalisio, Andrea Civra, Rebecca M. Broeckel, Nicole Haese, Paulo Jacob Silva, Randy P. Carney, Varpu Marjomäki, Daniel N. Streblow, David Lembo, Francesco Stellacci (), Vincenzo Vitelli () and Silke Krol
Additional contact information
Maria Pelliccia: European School of Molecular Medicine (SEMM), IFOM-IEO-Campus, via Adamello 16, Milan 20139, Italy
Patrizia Andreozzi: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
Jayson Paulose: Instituut-Lorentz for theoretical physics, Leiden University
Marco D’Alicarnasso: European School of Molecular Medicine (SEMM), IFOM-IEO-Campus, via Adamello 16, Milan 20139, Italy
Valeria Cagno: Laboratory of Molecular Virology and Antiviral Research, University of Turin, S. Luigi Gonzaga Hospital
Manuela Donalisio: Laboratory of Molecular Virology and Antiviral Research, University of Turin, S. Luigi Gonzaga Hospital
Andrea Civra: Laboratory of Molecular Virology and Antiviral Research, University of Turin, S. Luigi Gonzaga Hospital
Rebecca M. Broeckel: Vaccine & Gene Therapy Institute, Oregon Health & Science University
Nicole Haese: Vaccine & Gene Therapy Institute, Oregon Health & Science University
Paulo Jacob Silva: Institute of Materials and Interfaculty Bioengineering Institute, École polytechnique fédérale de Lausanne
Randy P. Carney: Institute of Materials and Interfaculty Bioengineering Institute, École polytechnique fédérale de Lausanne
Varpu Marjomäki: University of Jyväskyla
Daniel N. Streblow: Vaccine & Gene Therapy Institute, Oregon Health & Science University
David Lembo: Laboratory of Molecular Virology and Antiviral Research, University of Turin, S. Luigi Gonzaga Hospital
Francesco Stellacci: Institute of Materials and Interfaculty Bioengineering Institute, École polytechnique fédérale de Lausanne
Vincenzo Vitelli: Instituut-Lorentz for theoretical physics, Leiden University
Silke Krol: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta

Nature Communications, 2016, vol. 7, issue 1, 1-7

Abstract: 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 (10−8–10−6 M) or polyethylene glycol (PEG, molecular weight ∼8,000 Da, 10−7–10−4 M) 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.

Date: 2016
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DOI: 10.1038/ncomms13520

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