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
    • "Hence, heat resistant vaccine formulations have immense value during cold chain break-down (Levin et al., 2007). It is possible to prolong the shelf-life of most of the vaccines at lower temperatures (Chen and Kristensen, 2009). Thus, to determine the optimum conditions for storage of vaccine and its use in the field, the data on the stability of the vaccine is a requisite. "
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    ABSTRACT: The study describes the effect of stabilization on the stability of an indigenous live attenuated orf vaccine with stabilizers like LS, LHT and TAA after lyophilization and also reconstitution with NSS, PBS, distilled water and 1 M MgSO4 exposed at different temperatures under established lyophilization conditions. The stability of the vaccine was assessed both in freeze-dried and reconstituted forms at different temperatures. The results indicated that the orf vaccine lyophilized with LS stabilizer at 25 and 45°C and LHT at 37°C found superior over others in stabilizing the keeping quality of the vaccine. Intrinsic thermo-stability studies revealed the rapid deterioration of the vaccine, when compared to the vaccine stabilized with the either of the stabilizers. Among the diluents used for reconstitution of the vaccine, quality in terms of infectivity titers of the virus was well preserved in vaccine diluted with 0.85% NSS compared to other diluents like PBS, DW and 1 M MgSO4. The 1 M MgSO4 found unsuitable for diluting the orf vaccine. The study suggests that the LS at 25 and 45°C and LHT at 37°C are the choice of stabilizers and 0.85% NSS is the choice of diluent for orf vaccine at all temperatures contemplated.
    No preview · Article · Oct 2015 · Asian Journal of Animal and Veterinary Advances
    • "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.
    No preview · Article · May 2015 · Vaccine
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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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    ABSTRACT: In this study, thermostability of a Vero cell attenuated live camelpox vaccine under conventional lyophilization conditions has been evaluated. Three stabilizers were used separately for freeze-drying the vaccine and the stability of the vaccine, both in freeze-dried and reconstituted forms at different temperatures was assessed. The study revealed that the camelpox vaccine lyophilized with TAA stabilizer found superior with a shelf life of 44 months, 227 days, 22 days and 20 days at 4, 25, 37 and 45 °C, respectively followed by LS stabilizer. In terms of half-life, TAA stabilizer proved better followed by LS and BUGS stabilizers at all temperatures except at 25 °C in which LS found relatively superior. Among the four diluents viz. 1x PBS (phosphate buffered saline, pH 7.4), 0.85% NaCl, distilled water and 1 M MgSO4, PBS was a better diluent followed by 0.85% NaCl. Both the diluents maintained the infectivity titer more than the minimum effective dose (3 log10TCID50 with a maximum titre of 6.53 log10TCID50 in both the diluents) for 60 h at 37 and 45 °C. However, 1 M MgSO4 found less suitable for camelpox vaccine dilution. The study indicates that the TAA and 1× PBS are the choice of stabilizer and diluent, respectively for camelpox vaccine.
    Full-text · Article · May 2014 · Biologicals
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