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

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.