Developing a Stabilizing Formulation of a Live Chimeric Dengue Virus Vaccine Dry Coated on a High-Density Microarray Patch.

Jovin J Y Choo,Paul R Young,Germain J P Fernando,Christopher L D Mcmillan,David A Muller,Jody Hobson-Peters,Roy A Hall

doi:10.3390/vaccines9111301

Jovin J Y Choo, Paul R Young + Show 5 more

Open Access

https://doi.org/10.3390/vaccines9111301

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Abstract

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.

Highlights

Dengue is a systemic viral infection with approximately 390 million infections annually, of which 96 million result in disease of varying severity [1]
The C8 antigen was calibrated against an internal reference standard of stock bDENV2 produced in house
As antigenic integrity was judged by C8 binding, we developed a C8 antigen unit as a measure of vaccine potency

Summary

Introduction

Dengue is a systemic viral infection with approximately 390 million infections annually, of which 96 million result in disease of varying severity [1]. DENV infection results in a broad spectrum of symptoms, ranging from dengue fever (DF), a self-limiting illness, to severe dengue with plasma leakage, severe bleeding, or organ impairment [4]. With 3 billion people living in regions of virus transmission and the increased risk of viral transmission to travelers to endemic countries, the development of a vaccine against. While Dengvaxia licensure in 2016 has been a major advance in dengue vaccine development, limitations around its efficacy have required the ongoing development of alternative vaccines [6,7,8]

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