Journal
VACCINE
Volume 29, Issue 43, Pages 7456-7462Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2011.07.054
Keywords
Attenuated vaccine; Dengue; Flavivirus; Thermal stability; Recombinant viral vaccine
Categories
Funding
- NIH [1 U01 AI070443-01]
- Rocky Mountain Regional Centers for Excellence
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Thermal stability is important for the manufacture, distribution and administration of vaccines, especially in tropical developing countries, where particularly adverse field conditions exist. Current live-attenuated flavivirus vaccines exhibit relatively poor liquid stability in clinical settings, and clinicians are instructed to discard the yellow fever vaccine 1 h after reconstitution. We have identified novel combinations of excipients that greatly enhance the thermal stability of live-attenuated DEN-2 PDK-53-based flavivirus vaccine candidates. Liquid formulations comprising a sugar, albumin and a pluronic polymer minimized the loss of flavivirus infectious titer to less than 0.5 log(10) pfu after storage for at least 8 h at 37 degrees C, 7 days at room temperature or at least 11 weeks at 4 degrees C. Additionally, these formulations prevented reduction of viral infectivity after two freeze-thaw cycles of virus. Formulated candidate vaccines were readily lyophilized and reconstituted with minimal loss of viral titers. In mice, the formulations were safe and did not hinder the ability of the vaccine virus to generate a potent, protective immune response. These formulations provided significantly greater liquid-phase stability than has been reported previously for other flavivirus vaccine formulations. The enhanced thermal stability provided by the formulations described here will facilitate the effective distribution of flavivinis vaccines worldwide. (C) 2011 Elsevier Ltd. All rights reserved.
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