Developing a Stabilizing Formulation of a Live Chimeric Dengue Virus Vaccine Dry Coated on a High-Density Microarray Patch
Jovin J. Y. Choo,
Christopher L. D. McMillan,
Germain J. P. Fernando,
Roy A. Hall,
Paul R. Young,
Jody Hobson-Peters,
David A. Muller
Affiliations
Jovin J. Y. Choo
Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia
Christopher L. D. McMillan
Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia
Germain J. P. Fernando
Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia
Roy A. Hall
Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia
Paul R. Young
Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia
Jody Hobson-Peters
Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia
David A. Muller
Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia
Alternative delivery systems such as the high-density microarray patch (HD-MAP) are being widely explored due to the variety of benefits they offer over traditional vaccine delivery methods. As vaccines are dry coated onto the HD-MAP, there is a need to ensure the stability of the vaccine in a solid state upon dry down. Other challenges faced are the structural stability during storage as a dried vaccine and during reconstitution upon application into the skin. Using a novel live chimeric virus vaccine candidate, BinJ/DENV2-prME, we explored a panel of pharmaceutical excipients to mitigate vaccine loss during the drying and storage process. This screening identified human serum albumin (HSA) as the lead stabilizing excipient. When bDENV2-coated HD-MAPs were stored at 4 °C for a month, we found complete retention of vaccine potency as assessed by the generation of potent virus-neutralizing antibody responses in mice. We also demonstrated that HD-MAP wear time did not influence vaccine deposition into the skin or the corresponding immunological outcomes. The final candidate formulation with HSA maintained ~100% percentage recovery after 6 months of storage at 4 °C.
