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Formulation Approach that Enables the Coating of a Stable Influenza Vaccine on a Transdermal Microneedle Patch

  • Research Article
  • Theme: Recent Advances on Drug Delivery Systems for Viral Infections
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Abstract

A trivalent influenza split vaccine was formulated at high concentration for coating on the transdermal microneedle system. Monovalent vaccine bulks of three influenza strains, two influenza A strains, and one B strain were diafiltrated, concentrated, and lyophilized. The lyophilized powder of each vaccine strain was separately reconstituted and subsequently combined into a coating formulation of high concentration trivalent vaccine. The formulation process converted the monovalent vaccine bulks with low hemagglutinin (HA) concentrations 0.1 mg/mL into a viscous, emulsion containing HA at ~50 mg/mL. This physically stable emulsion demonstrated viscosity 1 poise and 30° contact angle for effective, homogeneous coating on each microneedle. Evaluation of the vaccine antigen HA by SRID and SDS-PAGE/Western blot showed that HA remained stable throughout the vaccine transdermal microneedle system manufacturing process and 1-year ambient storage (25°C). Anti-influenza antibody responses were evaluated by ELISA and hemagglutination inhibition (HAI) assay after primary and booster immunization with the vaccine-coated transdermal microneedle systems at either 25-μg or 40-μg total HA. The results showed the induction of serum anti-influenza IgG and anti-HA neutralizing antibodies after primary immunization and significant titer rises after booster immunization for both doses, indicating the dry-coated trivalent vaccine delivered by transdermal microneedle system elicited both primary and recall antibody responses against all three antigen strains. The study demonstrates that the transdermal microneedle system provides an attractive alternative for influenza vaccine delivery with key advantages such as preservative-free and room-temperature storage.

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Authors and Affiliations

  1. Zosano Pharma, Inc., 34790 Ardentech Court, Fremont, CA, 94555, USA

    Mahmoud Ameri, Yi Ao & Hayley Lewis

Authors
  1. Mahmoud Ameri
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  2. Yi Ao
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  3. Hayley Lewis
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Correspondence to Mahmoud Ameri.

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The authors declare that they have no conflict of interest and are all employees of Zosano Pharma.

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Guest Editor: Claudio Salomon

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Ameri, M., Ao, Y. & Lewis, H. Formulation Approach that Enables the Coating of a Stable Influenza Vaccine on a Transdermal Microneedle Patch. AAPS PharmSciTech 22, 175 (2021). https://doi.org/10.1208/s12249-021-02044-4

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  • DOI: https://doi.org/10.1208/s12249-021-02044-4

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