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

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.

Exploiting Unique Features of Microneedles to Modulate Immunity

“…Many recent MNA studies now incorporate rigorous screening processes for various amounts and types of excipients, such as carbohydrates and salts, to improve the immunogenicity of the vaccine. [214][215][216][217] In particular, including trehalose to stabilize hepatitis B vaccine (HBV) formulations maintained immunogenicity after storage at 40 °C for 7 d, as measured by antibody titers against the virus in mice. [218] In another example, the vaccinia virus, stabilized with PVA and trehalose, could be coated onto MNAs and stored at −20 °C for up to 30 d. After this time, it was still able to elicit significant levels of neutralizing antibodies compared to uncoated controls.…”

A chimeric vaccine protects saltwater crocodiles (Crocodylus porosus) from skin lesions caused by West Nile virus

“…The e cacy of BinJV-based chimeric vaccines in the prevention of avivirus infections has previously been demonstrated in various mouse models [21][22][23][24] .…”

Enhancement of cellular immunity following needle-free vaccination of mice with SARS-CoV-2 spike protein

“…The ongoing COVID-19 pandemic and the constant emergence of viral variants that escape pre-existing immunity necessitates the need for novel vaccines and vaccine delivery mechanisms. The HD-MAP presents an attractive alternative delivery mechanism, due to its ease of use, potent immune-enhancing activity, and thermostability, making it an ideal platform for global distribution [2][3][4]6]. We have previously demonstrated the HD-MAP's utility as a COVID-19 vaccine delivery platform, demonstrating single-dose protection when delivering a SARS-CoV-2 spike protein vaccine candidate, HexaPro, in a mouse challenge model [1].…”

“…This dynamic application is important to overcome variances in skin thickness and elasticity, especially in human subjects. Delivery of vaccines via the HD-MAP offers many advantages in terms of antigenicity and thermostability, resulting in significant dose-sparing and enhanced antibody kinetics for a wide range of vaccine modalities [1][2][3][4][5]. The dynamic application of the HD-MAP provides a physical adjuvant effect, with localised cell death and inflammation enhancing the immune response [6].…”