Soluble needle arrays for delivery of influenza vaccines
Inventors
O'Hagan, Derek • Singh, Manmohan • Kwon, Sung-Yun
Assignees
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Publication Number
US-9517205-B2
Publication Date
2016-12-13
Expiration Date
Abstract
Influenza vaccines are administered using solid biodegradable microneedles. The microneedles are fabricated from the influenza vaccine in combination with solid excipient(s) and, after penetrating the skin, they dissolve in situ and release the vaccine to the immune system. The influenza vaccine is (i) a purified influenza virus surface antigen vaccine, rather than a live vaccine or a whole-virus or split inactivated vaccine (ii) an influenza vaccine prepared from viruses grown in cell culture, not eggs, (iii) a monovalent influenza vaccine e.g. for immunizing against a pandemic strain, (iv) a bivalent vaccine, (v) a tetravalent or >4-valent vaccine, (vi) a mercury-free vaccine, or (vii) a gelatin-free vaccine.
Core Innovation
A skin patch is provided that includes a plurality of solid biodegradable microneedles. The microneedles comprise a biosoluble and biodegradable matrix material mixed with a purified influenza virus surface antigen vaccine comprising hemagglutinin, and the microneedles incorporate a detergent in a defined amount relative to hemagglutinin.
The approach is directed to influenza vaccination using soluble biodegradable microneedle arrays on a skin patch, where the solid microneedles retain integrity and then dissolve in situ. The influenza vaccine is described as inactivated and as purified influenza virus surface antigen vaccine, and the provided content includes cell-culture derived influenza products that reduce residual egg proteins and alter glycosylation while maintaining hemagglutinin content for immunogenicity.
The provided content further describes formulation breadth and quantitative constraints for the microneedle patch. Vaccine formats include monovalent, bivalent, tetravalent, or greater-than-4-valent formulations, with options such as mercury-free and gelatin-free vaccines, and defined detergent-to-hemagglutinin relationships.
Claims Coverage
The document provides three independent claim sets centered on a microneedle skin patch that uses a biosoluble and biodegradable matrix with a purified influenza virus surface antigen vaccine and a defined detergent-to-hemagglutinin amount ratio. Across the independent claims, four main inventive feature themes are emphasized: the microneedle patch composition, a preparation process into microneedle-forming cavities, selectable influenza vaccine types and hemagglutinin dose per patch, and the detergent formulation constraint.
Biosoluble biodegradable microneedle matrix mixed with purified influenza virus surface antigen vaccine at defined detergent-to-hemagglutinin ratio
A skin patch comprising a plurality of solid biodegradable microneedles wherein the microneedles comprise a biosoluble and biodegradable matrix material mixed with a purified influenza virus surface antigen vaccine comprising hemagglutinin and 5-30 μg of detergent per μg of hemagglutinin.
Mixing biosoluble biodegradable matrix with purified influenza virus surface antigen vaccine and molding microneedles
A process for preparing a skin patch comprising a plurality of solid biodegradable microneedles comprising mixing a biosoluble and biodegradable matrix material with a purified influenza virus surface antigen vaccine comprising hemagglutinin and 5-30 μg of detergent per μg of hemagglutinin, and adding the mixture to a mold containing cavities for forming microneedles.
Microneedle patch with hemagglutinin dose per patch under detergent-to-hemagglutinin ratio and defined influenza vaccine options
A skin patch comprising a plurality of solid biodegradable microneedles wherein the microneedles comprise a biosoluble and biodegradable matrix material mixed with a split influenza virus vaccine, a purified influenza virus surface antigen vaccine, an influenza virosomes vaccine, or a recombinant influenza virus surface antigen vaccine comprising an influenza virus hemagglutinin, wherein the amount of influenza virus hemagglutinin per patch is <16 μg per strain, and wherein the patch comprises 5-30 μg of detergent per μg of hemagglutinin.
Across the independent claims, the inventive coverage is concentrated on solid biodegradable microneedles incorporated into a skin patch with a biosoluble and biodegradable matrix and an influenza virus hemagglutinin-containing vaccine, while enforcing a detergent-to-hemagglutinin ratio of 5-30 μg detergent per μg hemagglutinin. The claims also cover preparing the patch by mixing and then introducing the mixture into a mold with microneedle cavities, and limiting the hemagglutinin amount per patch while allowing selected influenza vaccine variants.
Stated Advantages
Reported preclinical mouse immunization and challenge results indicate immune responses comparable to intramuscular injection at low hemagglutinin doses.
Reported improved survival and weight maintenance versus controls in challenge studies.
Documented Applications
Preclinical mouse immunization and challenge studies using intradermal administration of the influenza vaccine-loaded soluble microneedle skin patch with hemagglutination inhibition and neutralization titers.
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