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.
