Towards ambient temperature-stable vaccines: The identification of thermally stabilizing liquid formulations for measles virus using an innovative high-throughput infectivity assay

Schlehuber, Lisa D.; McFadyen, Iain; Shu, Yu-Chen; Carignan, James; Duprex, W. Paul; Forsyth, William R.; Ho, Jason H.; Kitsos, Christine M.; Lee, George Y.; Levinson, Douglas A.; Lucier, Sarah C.; Moore, Christopher; Nguyen, Niem Tu; Ramos, Josephine; Weinstock, B. André; Zhang, Mengjie; Monagle, Julie A.; Gardner, Colin; Álvarez, Juan Carlos

doi:10.1016/j.vaccine.2011.04.079

Cited by 54 publications

(33 citation statements)

References 25 publications

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“…Different vaccines within each of these categories have shown variable sensitivities (reviewed in [3–5]), although live attenuated organisms tend to be especially problematic. For example, most measles vaccines based on live viruses can only withstand exposure to 37°C for about 7 days [4]; some can lose potency by a factor of 10 after only 8h at 37°C [6]. Liquid-formulated oral poliovirus vaccines based on live attenuated virus are only stable at 37°C for two days [3,5].…”

Section: Introductionmentioning

confidence: 99%

Thermal stability of self-assembled peptide vaccine materials

et al. 2016

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The majority of current vaccines depend on a continuous “cold chain” of storage and handling between 2–8°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 7 days. 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.

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Section: Introductionmentioning

confidence: 99%

Thermal stability of self-assembled peptide vaccine materials

et al. 2016

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“…The development of thermally stable formulations for the major vaccines could relieve bottlenecks in the vaccine supply chain2. The addition of additives to existing vaccines usually means to get again through the costly process of approval by health authorities, which is commercially unattractive3. Therefore, proposing solutions that use inexpensive additives for stabilization increases the likelihood of their adoption by vaccine manufacturers in the development of new vaccines…”

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confidence: 99%

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

et al. 2016

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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.

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“…The poor efficacy and instability of vaccine products lead to incomplete immunization and a rapid loss of potency during storage and delivery, which severely limits the coverage of current vaccination programs. For example, ∼50% of vaccine products are finally discarded due to poor thermostability (5). Refrigeration is essential for vaccines to maintain their quality.…”

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confidence: 99%

Rational design of thermostable vaccines by engineered peptide-induced virus self-biomineralization under physiological conditions

Wang

Cao

Chen

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

145

127

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The development of vaccines against infectious diseases represents one of the most important contributions to medical science. However, vaccine-preventable diseases still cause millions of deaths each year due to the thermal instability and poor efficacy of vaccines. Using the human enterovirus type 71 vaccine strain as a model, we suggest a combined, rational design approach to improve the thermostability and immunogenicity of live vaccines by self-biomineralization. The biomimetic nucleating peptides are rationally integrated onto the capsid of enterovirus type 71 by reverse genetics so that calcium phosphate mineralization can be biologically induced onto vaccine surfaces under physiological conditions, generating a mineral exterior. This engineered self-biomineralized virus was characterized in detail for its unique structural, virological, and chemical properties. Analogous to many exteriors, the mineral coating confers some new properties on enclosed vaccines. The self-biomineralized vaccine can be stored at 26°C for more than 9 d and at 37°C for approximately 1 wk. Both in vitro and in vivo experiments demonstrate that this engineered vaccine can be used efficiently after heat treatment or ambient temperature storage, which reduces the dependence on a cold chain. Such a combination of genetic technology and biomineralization provides an economic solution for current vaccination programs, especially in developing countries that lack expensive refrigeration infrastructures.genetic engineering | vaccine design | shell

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Towards ambient temperature-stable vaccines: The identification of thermally stabilizing liquid formulations for measles virus using an innovative high-throughput infectivity assay

Cited by 54 publications

References 25 publications

Thermal stability of self-assembled peptide vaccine materials

Thermal stability of self-assembled peptide vaccine materials

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

Rational design of thermostable vaccines by engineered peptide-induced virus self-biomineralization under physiological conditions

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