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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 (10-8-10-6?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.

SUBMITTER: Pelliccia M

PROVIDER: S-EPMC5141364 | biostudies-other | 2016 Nov

REPOSITORIES: biostudies-other

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

Pelliccia Maria M Andreozzi Patrizia P Paulose Jayson J D'Alicarnasso Marco M Cagno Valeria V Donalisio Manuela M Civra Andrea A Broeckel Rebecca M RM Haese Nicole N Jacob Silva Paulo P Carney Randy P RP Marjomäki Varpu V Streblow Daniel N DN Lembo David D Stellacci Francesco F Vitelli Vincenzo V Krol Silke S

Nature communications 20161130

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<su ...[more]

PMID: 27901019

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Project description:The majority of current vaccines depend on a continuous "cold chain" of storage and handling between 2 and 8°C. Vaccines experiencing temperature excursions outside this range can suffer from reduced potency. This thermal sensitivity results in significant losses of vaccine material each year and risks the administration of vaccines with diminished protective ability, issues that are heightened in the developing world. Here, using peptide self-assemblies based on the fibril-forming peptide Q11 and containing the epitopes OVA323-339 from ovalbumin or ESAT651-70 from Mycobacterium tuberculosis, the chemical, conformational, and immunological stability of supramolecular peptide materials were investigated. It was expected that these materials would exhibit advantageous thermal stability owing to their adjuvant-free and fully synthetic construction. Neither chemical nor conformational changes were observed for either peptide when stored at 45°C for 7days. ESAT651-70-Q11 was strongly immunogenic whether it was stored as a dry powder or as aqueous nanofibers, showing undiminished immunogenicity even when stored as long as six months at 45°C. This result was in contrast to ESAT651-70 conjugated to a protein carrier and adjuvanted with alum, which demonstrated marked thermal sensitivity in these conditions. Antibody titers and affinities were undiminished in mice for OVA323-339-Q11 if it was stored as assembled nanofibers, yet some diminishment was observed for material stored as a dry powder. The OVA study was done in a different mouse strain and with a different prime/boost regimen, and so it should not be compared directly with the study for the ESAT epitope. This work indicates that peptide self-assemblies can possess attractive thermal stability properties in the context of vaccine development.Almost all current vaccines must be maintained within a tight and refrigerated temperature range, usually between 2 and 8°C. This presents significant challenges for their distribution, especially in the developing world. Here we report on the surprisingly robust thermal stability of a self-assembled peptide vaccine. In particular a self-assembled peptide vaccine containing a tuberculosis epitope maintained all of its potency in mice when exposed to an extreme thermal treatment of six months at 45°C. In a different mouse model, we investigated another model epitope and found some storage conditions where potency was diminished. Overall this study illustrates that some self-assembled peptide vaccines can have remarkable thermal stability.

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

Publications

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

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