Development of an Immunogenic Spray-Freeze-Dried Powder Vaccine Against SARS-CoV-2
Harry W. Pan1, Jian-Piao Cai2, Kwok-Yung Yuen2, Jenny K.W. Lam1,3
1Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong
2Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong
3Department of Pharmaceutics, UCL School of Pharmacy, University College London
Summary
After more than two years of experience with SARS-CoV-2, a suite of vaccines has become available as part of the global efforts to contain the rapid spread and devastating impact of the pandemic. Like many other liquid vaccines, currently approved COVID-19 vaccines are intramuscular injections. While this invasive route of administration has acquired strong evidence of efficacy, other delivery methods may be more advantageous. In the context of COVID-19, mucosal immunity in the respiratory tract would be highly beneficial, given that is it typically the first point of viral entry. In this study, a dry powder vaccine based on the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein was developed for intranasal inhalation. Spray-freeze-drying with an ultrasonic nozzle was applied to produce porous particles adequate for aerosolisation to the nasal airway. The formulation was a mixture of the antigen, aluminium hydroxide gel as adjuvant, and 2-hydroxypropyl-beta-cyclodextrin as cryoprotective and lyoprotective agent. The spray-freeze-dried powder was characterised in terms of particle size by laser diffraction and morphology by scanning electron microscopy. The median volume diameter of the spherical particles was approximately 38 µm, which is suitable for nasal deposition in humans. The antigen-adjuvant binding efficiency measured by polyacrylamide gel electrophoresis was 68%, a reduction from 87% before drying. Preliminary in vivo assessment of the vaccine delivered via intratracheal administration induced remarkable immune responses in mice. Together, the results indicate that this solid-state vaccine possesses physical characteristics appropriate for intranasal delivery and is a promising alternative to parenteral COVID-19 vaccines.
Key Message
A protein subunit vaccine targeting the RBD of the SARS-CoV-2 spike protein produced by spray-freeze-drying was capable of eliciting humoral immune response in mice following intratracheal delivery. This illustrates the possibility of administering immunogenic and efficacious COVID-19 vaccines via a noninvasive route without the existing logistical challenges.