Comparable Immunogenicity of 2P and 6P Proline Stabilization Strategies in mRNA Vaccines Against SARS-CoV-2 KP.2 Variant

다국어 초록 (Multilingual Abstract)

The SARS-CoV-2 Omicron subvariant KP.2 harbors the V1104L mutation in the S2 region, which may affect spike protein structural stability. Proline-based stabilization strategy is a key strategy for the development of SARS-CoV-2 mRNA vaccines, with previous studies reporting superior immunogenicity of six proline (6P) over two proline (2P) stabilization. However, it was studied in the early mutants and not in the latest mutants in which the S2 mutation occurred. Therefore, in this study we compared wild type, 2P (K986P, V987P), and 6P (F817P, A892P, A899P, K986P, V987P, A942P) mRNA vaccine constructs targeting KP.2 spike protein in vitro and murine immunization model. in vitro protein expression analysis revealed that both 2P and 6P variants exhibited increased expression compared to wild type with no difference between proline variants. Following immunization, neutralizing antibody titers between 2P and 6P groups were comparable between 2P and 6P groups, both showing superior responses to WT. Additionally, IFN-γ secreting T cells were higher and similarly induced in the proline stabilizing group compared to the wild type. These finding contrast with previous findings of 6P superiority in ancestral strains. These 2P and 6P immunogenicity equivalents of KP.2 suggest the possibility that the V1104L mutation in the S2 region was involved in structural stabilization. Our findings indicate that there may be differences in immunogenicity according to vaccine strategy among strains, and demonstrate the need for structure-based vaccine optimization for novel SARS-CoV-2 strains.

목차 (Table of Contents)

• Ⅰ. Abstract 1
• Ⅱ. Introduction 3
• Ⅲ. Materials and Methods 10
• Ⅳ. Results 18
• Ⅴ. Discussion 36
• Ⅶ. References 42
• Ⅷ. 국문 논문제출서 48
• Ⅸ. 국문 인준서 49
• Ⅹ. 국문 초록 50