An mRNA vaccine against SARS-CoV-2: Lyophilized, liposome-based vaccine candidate EG-COVID induces high levels of virus neutralizing antibodies

Abstract

In addition to the traditional method of vaccine development, the mRNA coronavirus vaccine, which is attractive as a challenging vaccination, recently opened a new era in vaccinology. Here we describe the EG-COVID which is a novel liposome-based mRNA candidate vaccine that encodes the spike (S) protein of SARS-CoV-2 with 2P-3Q substitution in European variant. We developed the mRNA vaccine platform that can be lyophilized using liposome-based technology. Intramuscular injection of the EG-COVID elicited robust humoral and cellular immune response to SARS-CoV-2. Furthermore, sera obtained from mice successfully inhibited SARS-CoV-2 viral infection into Vero cells. We developed EG-COVID and found it to be effective based on in vitro data, and we plan to initiate a clinical trial soon. Since EG-COVID is a lyophilized mRNA vaccine that is convenient for transportation and storage, accessibility to vaccines will be significantly improved.

Challenges of Storage and Stability of mRNA-Based COVID-19 Vaccines

“…Degradation of mRNA is higher in the presence of water, which makes liposomes less likely to be stable than LNP [14]. Notably, a stable mRNA vaccine was developed with liposomes [42], but it is not known whether the shelf life of liposomal vaccines will be longer than LNP vaccines.…”

Lyophilization provides long-term stability for a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine

“…Recent studies have shown that LNPs containing small interfering (si) RNA or mRNA can be successfully lyophilized. [8][9][10] Tekmira Pharmaceuticals developed an LNP for treatment of Zaire Ebola virus (ZE-BOV) infection containing siRNA targeting VP24, VP35, and L polymerase proteins. 11,12 After demonstrating complete protection of non-human primates (NHPs) in an otherwise lethal model of ZE-BOV, a reformulated, lyophilized version (TKM-100802) was assessed in a phase 1 clinical trial in 2014 (NCT02041715).…”

“…8 Two recent studies demonstrated that the mRNA-LNP platform can also be lyophilized. 9,10 Zhao et al generated lyophilized firefly luciferase-encoding mRNA-LNPs and demonstrated that the reconstituted material maintains the mRNA expression efficiency in mice as observed with in vivo bioluminescence imaging studies. 9 Hong et al developed a lyophilized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA-LNP vaccine formulation and showed that the reconstituted vaccine can induce strong immune responses in mice.…”

Bioengineering Strategies for Developing Vaccines against Respiratory Viral Diseases

“…The study is currently in phase 2/3 clinical trials (ClinicalTrials.gov identifiers NCT04652102 and NCT04674189). A similar vaccine was made by Hong et al using full-length SARS-CoV-2 S-encoding mRNA of the more infectious and fatal variant D614G ( 146 ). The uniqueness of this vaccine is that it can be lyophilized without loss of immunogenicity and is, therefore, highly advantageous for storage and distribution ( 146 ).…”