1. Development of a Freeze-Dried, Heat-Stable Influenza Subunit Vaccine Formulation.
- Author
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Flood A, Estrada M, McAdams D, Ji Y, and Chen D
- Subjects
- Animals, Crystallization, Crystallography, X-Ray, Excipients, Female, Humans, Humidity, Influenza A Virus, H1N1 Subtype immunology, Influenza, Human immunology, Mice, Inbred BALB C, Orthomyxoviridae Infections immunology, Powders, Chemistry, Pharmaceutical methods, Freeze Drying, Hot Temperature, Influenza Vaccines immunology, Vaccines, Subunit immunology
- Abstract
An influenza pandemic remains a major public health concern. A key strategy to prevent a pandemic is to stockpile and pre-position stable influenza vaccine to allow rapid deployment in response to an outbreak. However, most influenza vaccines today are formulated as liquids that are stable only within a temperature range of 2°C to 8°C and require use of a cold chain, making vaccine transportation, distribution, and storage complicated and expensive, particularly for developing countries. To support the National Strategy for Pandemic Influenza preparedness in the United States and internationally, we developed two lead dry formulations of stable H1N1 influenza subunit vaccines using freeze-drying technology. The stable formulations contain an excipient combination of a disaccharide, such as sucrose or trehalose, and glycine, in addition to a surfactant and phosphate buffer. The freeze-dried vaccines were shown to be safe and remained immunogenic in an in vivo study in mice. Moreover, the lead formulations demonstrated no significant loss of activity after 40 months at storage temperatures of 25°C and 37°C. This stability can be particularly attractive as it could eliminate the need to use a cold chain for vaccine deployment and facilitate integration of vaccine distribution with general drug distribution where appropriate. These freeze-dried thermostable influenza subunit vaccines could also reduce the frequency of vaccine stockpile turnover, offering a cost-effective option for pandemic preparedness., Competing Interests: We have the following interests. Novartis Pharmaceuticals (East Hanover, NJ) provided the generous supply of two lots of influenza H1N1 subunit bulk vaccine for this study. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.
- Published
- 2016
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