Long-Term Protection from SARS-CoV-2 Variants in Mice by a Phase II Clinically Evaluated Original mRNA Vaccine Booster

Abstract

Objective: The global coronavirus disease 2019 (COVID-19) pandemic was caused by SARS-CoV-2. The authors developed an mRNA vaccine (LVRNA009) that encoded the S protein of the Wuhan-Hu-1 strain and evaluated the long-term protection potential against SARS-CoV-2 variants. Methods: Mice were initially vaccinated with 2 doses of LVRNA009, then boosted 8 months later. The virus neutralization titers against SARS-CoV-2 variants and antigen-specific T cell responses of the mice were determined. These animals were also tested using viral challenge experiments. Moreover, a phase II clinical study was carried out in 420 healthy adults. Results: LVRNA009 vaccination induced neutralization antibodies and protected mice from SARS-CoV-2 original and Omicron BA.1.1 challenge 8 months post-boosting. A second booster dose of LVRNA009 further enhanced VNTs against Omicron variants. Clinical studies showed that LVRNA009 has good safety and immunogenicity profiles in humans. Conclusion: LVRNA009 could provide long-term protection against SARS-CoV-2 variants and confer better protection with a booster dose. These findings indicate that LVRNA009, a vaccine designed based on the original virus, might be effective in management of the COVID-19 pandemic.