Heterologous Prime-Boost with Immunologically Orthogonal Protein Nanoparticles for Peptide Immunofocusing

Area of Science:

• Vaccine development
• Nanotechnology
• Immunology

Background:

• Protein nanoparticles serve as effective platforms for antigen presentation and immune cell targeting in vaccine design.
• Encapsulins are microbial nanocompartments that self-assemble into icosahedral structures and possess inherent immunogenic and self-adjuvanting properties, especially when packaging RNA.
• The SARS-CoV-2 receptor binding domain (RBD) is a key target for vaccine development.

Approach:

• Genetically engineered encapsulins from *Mxyococcus xanthus* to display a 20-mer peptide from a SARS-CoV-2 RBD mutant on their surface.
• Utilized bacterial RNA packaging within encapsulins to enhance immunogenicity.
• Implemented a heterologous prime/boost vaccination strategy using engineered encapsulins and PP7 virus-like particles.

Key Points:

• The engineered encapsulin successfully presented the SARS-CoV-2 RBD peptide, eliciting conformationally relevant humoral responses.
• RNA packaging within the encapsulins enhanced their immunogenic and self-adjuvanting properties.
• A prime/boost strategy with orthogonal nanoparticles led to selective antibody responses against a SARS-CoV-2 RBD point mutant.

Conclusions:

• Protein nanoparticles, specifically engineered encapsulins, are viable platforms for presenting viral antigens like the SARS-CoV-2 RBD.
• The use of orthogonal nanoparticles in a prime/boost regimen allows for fine-tuning of epitope-focused antibody responses.
• This approach demonstrates a method for controlling the specificity of antibody generation against viral targets.