A modular vaccine platform for optimized lipid nanoparticle mRNA immunogenicity.

Area of Science:

• Vaccinology
• Immunology
• Molecular Biology

Background:

• Messenger RNA (mRNA) vaccines face challenges in antigen cell surface translocation (CST), limiting immune response.
• Optimizing antigen expression and presentation is crucial for enhancing mRNA vaccine efficacy.

Purpose of the Study:

• To develop a modular vaccine platform (MVP) to improve the immunogenicity of challenging mRNA antigens.
• To enhance cell surface translocation (CST) and optimize antigen presentation for mRNA vaccines.

Main Methods:

• Developed a modular vaccine platform (MVP) enabling modular assembly of chimeric antigens with >2,500 combinations.
• Quantified CST efficacy of various modules using mpox virus (MPXV) proteins (A29, M1R, A35R) and other antigens.
• Assessed chimeric antigen surface expression in multiple cell lines and evaluated immune responses in vivo.

Main Results:

• Identified optimal CST modules that significantly enhance the immunogenicity of multiple MPXV antigens.
• Demonstrated improved immune responses and protection against lethal viral challenge using lipid nanoparticle mRNAs with MVP.
• Validated MVP's generalizability by optimizing human papillomavirus (HPV) and varicella zoster virus (VZV) antigens.

Conclusions:

• The modular vaccine platform (MVP) effectively enhances CST and immunogenicity of challenging mRNA antigens.
• MVP facilitates the development of more potent mRNA vaccines against diverse viral pathogens.
• This platform offers a versatile approach for advancing mRNA vaccine technology for various applications.