Opportunities and challenges of developing thermostable vaccines

PATH, Seattle, WA 98107, USA.
Expert Review of Vaccines (Impact Factor: 4.21). 06/2009; 8(5):547-57. DOI: 10.1586/erv.09.20
Source: PubMed


All vaccines lose potency over time and the rate of potency loss is temperature-dependent. Therefore, cold-chain systems have been established to ensure that the potency of vaccines is maintained by storing them under refrigerated conditions (in most cases between 2 and 8 degrees C) until the point of use. This article aims to review the approaches being used to develop thermostable vaccine formulations that would be resistant to damage caused by freezing or excessive heat, and that could reduce dependence on the cold chain. The challenges associated with the implementation of these novel formulations are discussed, as well as the potential benefits and opportunities of taking vaccines out of the cold chain.

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Available from: Debra Dawn Kristensen, Jan 02, 2014
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    • "refrigerated facilities for transportation and storage are often inadequate [14]. As an alternative to the current type-specific HPV vaccines, we have developed vaccines that target highly conserved, broadly neutralizing epitopes from the HPV minor capsid protein, L2 [9,15–18]. "
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    ABSTRACT: An ideal prophylactic human papillomavirus (HPV) vaccine would provide broadly protective and long-lasting immune responses against all high-risk HPV types, would be effective after a single dose, and would be formulated in such a manner to allow for long-term storage without the necessity for refrigeration. We have developed candidate HPV vaccines consisting of bacteriophage virus-like particles (VLPs) that display a broadly neutralizing epitope derived from the HPV16 minor capsid protein, L2. Immunization with 16L2 VLPs elicited high titer and broadly cross-reactive and cross-neutralizing antibodies against diverse HPV types. In this study we introduce two refinements for our candidate vaccines, with an eye towards enhancing efficacy and clinical applicability in the developing world. First, we assessed the role of antigen dose and boosting on immunogenicity. Mice immunized with 16L2-MS2 VLPs at doses ranging from 2 to 25μg with or without alum were highly immunogenic at all doses; alum appeared to have an adjuvant effect at the lowest dose. Although boosting enhanced antibody titers, even a single immunization could elicit strong and long-lasting antibody responses. We also developed a method to enhance vaccine stability. Using a spray dry apparatus and a combination of sugars & an amino acid as protein stabilizers, we generated dry powder vaccine formulations of our L2 VLPs. Spray drying of our L2 VLPs did not affect the integrity or immunogenicity of VLPs upon reconstitution. Spray dried VLPs were stable at room temperature and at 37°C for over one month and the VLPs were highly immunogenic. Taken together, these enhancements are designed to facilitate implementation of a next-generation VLP-based HPV vaccine which addresses U.S. and global disparities in vaccine affordability and access in rural/remote populations. Copyright © 2015. Published by Elsevier Ltd.
    Vaccine 05/2015; 33(29). DOI:10.1016/j.vaccine.2015.05.016 · 3.62 Impact Factor
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    • "All rights reserved. Biologicals xxx (2014) 1e7 Please cite this article in press as: Prabhu M, et al., Evaluation of stability of live attenuated camelpox vaccine stabilized with different stabilizers and reconstituted with various diluents, Biologicals (2014), longer at 2e8 C is possible [22]. However, the sensitivity of vaccines to excursions outside this range varies widely. "
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    Scientific Reports 04/2014; 4:4729. DOI:10.1038/srep04729 · 5.58 Impact Factor
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