Virus-like structures for combination antigen protein mRNA vaccination

Area of Science:

• Immunology and Vaccinology
• Nanotechnology in Medicine
• Virology and Infectious Diseases

Background:

• Effective vaccination necessitates advanced antigen delivery systems and robust immune activation.
• Current vaccine technologies face challenges in optimizing antigen presentation and eliciting broad immune responses.
• The emergence of SARS-CoV-2 variants highlights the need for adaptable and potent vaccine platforms.

Purpose of the Study:

• To develop and evaluate a novel lipid nanoparticle-based virus-like particle (VLP) system for enhanced antigen delivery.
• To investigate the VLP system's capacity to deliver both mRNA and protein antigens, specifically targeting SARS-CoV-2 variants.
• To assess the immune response generated by the combined mRNA-protein VLP vaccine compared to single-component vaccines.

Main Methods:

• Engineered lipid nanoparticles decorated with SARS-CoV-2 spike proteins (Omicron BA.1 S1) to form VLPs.
• Utilized VLPs to co-deliver mRNA encoding the S1 protein of a different SARS-CoV-2 variant (XBB.1) and S1 protein itself.
• Assessed VLP interaction with human respiratory epithelial cells and macrophages via ACE2 and DC-SIGN receptors.
• Evaluated macrophage and dendritic cell activation through receptor binding.
• Measured antibody responses in BALB/c mice following vaccination with the VLP system, mRNA alone, or protein alone.

Main Results:

• The VLP system successfully carried and delivered both mRNA and protein antigens.
• Surface S1 protein on VLPs facilitated targeted delivery and enhanced mRNA expression in specific immune cells.
• Receptor binding (ACE2, DC-SIGN) mediated by surface S1 protein activated macrophages and dendritic cells.
• The combined mRNA-protein VLP vaccine elicited a significantly higher antibody response in mice compared to monovalent mRNA or protein vaccines.
• Immune response mechanisms suggested cross-presentation to diverse dendritic cell subsets, bridging innate and adaptive immunity.

Conclusions:

• The developed VLP system represents a potent platform for co-delivering mRNA and protein antigens, enhancing vaccine efficacy.
• Targeted delivery and immune cell activation via specific receptor interactions contribute to the robust immune response.
• This strategy holds promise for developing next-generation vaccines against SARS-CoV-2 variants and potentially other infectious diseases.