title: Development of a Freeze-Dried, Heat-Stable Influenza Subunit Vaccine Formulation.
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.
authors.affiliation: Devices and Tools Program, PATH, Seattle, Washington, United States of America.
authors.forename: Alexander
authors.initials: A
authors.lastname: Flood
authors.affiliation: Devices and Tools Program, PATH, Seattle, Washington, United States of America.
authors.forename: Marcus
authors.initials: M
authors.lastname: Estrada
authors.affiliation: Devices and Tools Program, PATH, Seattle, Washington, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: McAdams
authors.affiliation: Drug Development Program, PATH, Seattle, Washington, United States of America.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Devices and Tools Program, PATH, Seattle, Washington, United States of America.
authors.forename: Dexiang
authors.initials: D
authors.lastname: Chen
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003460:Crystallization; D018360:Crystallography, X-Ray; D005079:Excipients; D005260:Female; D005612:Freeze Drying; D006358:Hot Temperature; D006801:Humans; D006813:Humidity; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology; D011208:Powders; D022223:Vaccines, Subunit / Q000276:immunology*
chemical_list: D005079:Excipients; D007252:Influenza Vaccines; D011208:Powders; D022223:Vaccines, Subunit