Design and development of a novel, thermostable, and inhalable dry powder COVID-19 vaccine

Summary Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) is a highly infectious virus known to cause the 2019 coronavirus disease (COVID-19). The disease has been declared as a global pandemic by the World Health Organization. In the United States, as of January 20, 2021, we have more than 24 million infected individuals with approximately 400,000 deaths. COVID-19 appears to be more deadly in patients with co-morbidities such as hypertension and diabetes and presents many clinical manifestations such as pneumonia, diarrhea, multiple organ failure, etc. among those infected. Moreover, the number of infections and fatality rate is expected to increase significantly over the next few months, according to the IHME model. There is an urgent global need to develop a thermostable and self-administrable vaccine. The spike protein on the surface of coronavirus is an excellent candidate for developing vaccines, has been used in the currently EUA obtained vaccines, as it plays an important role in the entry of the virus into the host cell. Liposomes are excellent drug delivery systems that can present the antigen as particulate in nature and allow the incorporation of an adjuvant that aids in the generation of a robust immune response. Further, the liposomes can be designed to be of similar size to that of the virus and the spike protein can be conjugated to the liposomal surface to mimic the natural presentation on the virus. The immune cells will internalize and process the antigen like the virus and generate neutralizing antibody titers. Most of the vaccines currently in the market require cold chain (refrigeration) to store and distribute the vaccine to maintain the efficacy and require a visit to the clinic for immunization by trained medical personnel. These serve as bottlenecks in achieving mass vaccination in a pandemic adding further stress to the hospitals and the supply chain. In addition, a major limitation is the limited ability of existing manufacturing facilities to manufacture billions of doses. In this proposal, we aim to develop a thermostable and inhalable dry powder vaccine that is easy to scale-up, eliminates the need for cold-chain storage and transport, and is self-administrable by individuals' at-home by simple inhalation. To achieve this goal, we will pursue two aims: 1) Formulation of an inhalable and thermostable dry powder COVID-19 vaccine containing S protein-adsorbed liposomal carriers and 2) Evaluation of neutralizing mucosal and systemic IgA and IgG antibody titers after aerosol administration of dry powder COVID-19 vaccine in mice. Successful completion of this project will have a profound impact on the development of dry powder COVID-19 vaccine, particularly in exploring thermostable and inhalable vaccines that are easy to manufacture, store, and distribute, characteristics that are critical in pandemic.