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Thermal stability of self-assembled peptide vaccine materials
Open accessAbstract
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. Statement of significance 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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References 29 · Cited by 76
Research works printed but not linked: 29
- Chen, 2011, Improving the reach of vaccines to low-resource regions, with a needle-free vaccine delivery device and long-term thermostabilization, J. Controlled Release, 152, 349, 10.1016/j.jconrel.2011.02.026 · DOI
- Das, 2004, Revolutionary vaccine technology breaks the cold chain, Lancet Infect. Dis., 4, 719, 10.1016/S1473-3099(04)01222-8 · DOI
- Chen, 2009, Opportunities and challenges of developing thermostable vaccines, Expert Rev. Vaccines, 8, 547, 10.1586/erv.09.20 · DOI
- Kristensen, 2011, Vaccine stabilization: research, commercialization, and potential impact, Vaccine, 29, 7122, 10.1016/j.vaccine.2011.05.070 · DOI
- Schlehuber, 2011, Towards ambient temperature-stable vaccines: the identification of thermally stabilizing liquid formulations for measles virus using an innovative high-throughput infectivity assay, Vaccine, 29, 5031, 10.1016/j.vaccine.2011.04.079 · DOI
- Van Damme, 1992, Heat stability of a recombinant DNA hepatitis B vaccine, Vaccine, 10, 366, 10.1016/0264-410X(92)90064-Q · DOI
- Van Damme, 2012, Chapter 16, hepatitis B vaccine, 205
- Braun, 2009, Development of a freeze-stable formulation for vaccines containing aluminum salt adjuvants, Vaccine, 27, 72, 10.1016/j.vaccine.2008.10.027 · DOI
- Zhang, 2012, Stabilization of vaccines and antibiotics in silk and eliminating the cold chain, Proc. Natl. Acad. Sci. U.S.A., 109, 11981, 10.1073/pnas.1206210109 · DOI
- Wang, 2013, Rational design of thermostable vaccines by engineered peptide-induced virus self-biomineralization under physiological conditions, Proc. Natl. Acad. Sci. U.S.A., 110, 7619, 10.1073/pnas.1300233110 · DOI
- Wolff, 2008, Protection of aluminum hydroxide during lyophilisation as an adjuvant for freeze-dried vaccines, Colloids Surf. A, 330, 116, 10.1016/j.colsurfa.2008.07.031 · DOI
- Rudra, 2010, A self-assembling peptide acting as an immune adjuvant, Proc. Natl. Acad. Sci. U.S.A., 107, 622, 10.1073/pnas.0912124107 · DOI
- Chesson, 2014, Antigenic peptide nanofibers elicit adjuvant-free CD8+ T cell responses, Vaccine, 32, 1174, 10.1016/j.vaccine.2013.11.047 · DOI
- Pompano, 2014, Titrating T-cell epitopes within self-assembled vaccines optimizes CD4+ helper T cell and antibody outputs, Adv. Healthcare Mater., 3, 1898, 10.1002/adhm.201400137 · DOI
- Chen, 2013, The use of self-adjuvanting nanofiber vaccines to elicit high-affinity B cell responses to peptide antigens without inflammation, Biomaterials, 34, 8776, 10.1016/j.biomaterials.2013.07.063 · DOI
- Rudra, 2012, Modulating adaptive immune responses to peptide self-assemblies, ACS Nano, 6, 1557, 10.1021/nn204530r · DOI
- Hudalla, 2014, Gradated assembly of multiple proteins into supramolecular nanomaterials, Nat. Mater., 13, 829, 10.1038/nmat3998 · DOI
- Jung, 2010, Fibrillar peptide gels in biotechnology and biomedicine, Biopolymers, 94, 49, 10.1002/bip.21326 · DOI
- Harboe, 1998, B-cell epitopes and quantification of the ESAT-6 protein of Mycobacterium tuberculosis, Infect. Immun., 66, 717, 10.1128/IAI.66.2.717-723.1998 · DOI
- Jung, 2009, Co-assembling peptides as defined matrices for endothelial cells, Biomaterials, 30, 2400, 10.1016/j.biomaterials.2009.01.033 · DOI
- Jung, 2008, Modulating the mechanical properties of self-assembled peptide hydrogels via native chemical ligation, Biomaterials, 29, 2143, 10.1016/j.biomaterials.2008.01.008 · DOI
- Manning, 1988, Circular-dichroism studies of distorted alpha-helices, twisted beta-sheets, and beta-turns, Biophys. Chem., 31, 77, 10.1016/0301-4622(88)80011-5 · DOI
- Kumar, 1982, Studies on the stability of tetanus and pertussis components of DPT vaccine on exposure to different temperatures, Indian J. Pathol. Microbiol., 25, 50
- Gasiorowski, 2011, Directed Intermixing in multicomponent self-assembling biomaterials, Biomacromolecules, 12, 3549, 10.1021/bm200763y · DOI
- Hudalla, 2014, A self-adjuvanting supramolecular vaccine carrying a folded protein antigen, Adv. Healthcare Mater., 2, 1114, 10.1002/adhm.201200435 · DOI
- Rudra, 2012, Self-assembled peptide nanofibers raising durable antibody responses against a malaria epitope, Biomaterials, 33, 6476, 10.1016/j.biomaterials.2012.05.041 · DOI
- Vordermeier, 2007, Assessment of cross-reactivity between Mycobacterium bovis and M. kansasii ESAT-6 and CFP-10 at the T-cell epitope level, Clin. Vaccine Immunol., 14, 1203, 10.1128/CVI.00116-07 · DOI
- Olsen, 2000, Efficient protection against Mycobacterium tuberculosis by vaccination with a single subdominant epitope from the ESAT-6 antigen, Eur. J. Immunol., 30, 1724, 10.1002/1521-4141(200006)30:6<1724::AID-IMMU1724>3.0.CO;2-A · DOI
- Kim, 1972, Long-term preservation and storage of mycobacteria, Appl. Microbiol., 24, 311, 10.1128/AEM.24.3.311-317.1972 · DOI
Metadata
- Authors
- Sun, T., Han, H., Hudalla, G. A., Wen, Y., Pompano, R. R., & Collier, J. H.
- Affiliations
- University of Chicago (US)
- Corresponding author
- Collier, Joel H.
- Venue
- Acta Biomaterialia
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 30
- Pages
- 62-71
- ISSN
- 1742-7061 (ISSN-L)
- PMC
- PMC4821069
- OpenAlex
- W2239748356
- Cited by
- 76
- References
- 29
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 7 · 2023: 3 · 2022: 7 · 2021: 14 · 2020: 7 · 2019: 10 · 2018: 8 · 2017: 7 · 2016: 8
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Acta Biomaterialia (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Bill and Melinda Gates Foundation (OPP1061315)
- National Institutes of Health (1R01EB009801, 1R01AI118182)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Supramolecular Self-Assembly in Materials
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- peptide self-assembly, peptide vaccine, thermal stability, nanofibers, adjuvant-free vaccine, ovalbumin epitope, Mycobacterium tuberculosis, vaccine storage, immunogenicity, antibody titers
- MeSH terms
- Animals, Antigens, Bacterial, Bacterial Proteins, Female, Mycobacterium tuberculosis, Peptides, Tuberculosis Vaccines, Mice, Nanofibers
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