Effective Multivalent Oriented Presentation of Meningococcal NadA Antigen Trimers by Self-Assembling Ferritin...

Area of Science:

• Biotechnology
• Vaccinology
• Structural Biology

Background:

• Nanoparticle-displayed viral antigens mimic virions, enhancing humoral responses.
• Bacterial antigens on self-assembling protein nanoparticles also show potent immunogenicity.
• This highlights nanoparticles as a universal platform for vaccine development.

Purpose of the Study:

• To design, structurally analyze, and assess the immunogenicity of self-assembling ferritin nanoparticles displaying Neisseria meningitidis NadA.
• To evaluate the efficacy of these nanoparticles in eliciting antibody responses and bactericidal activity.

Main Methods:

• Engineered ferritin fusion constructs with NadA fragments (head only, head with stalk).
• Expressed constructs in Escherichia coli and confirmed self-assembly into nanoparticles via Cryo-electron microscopy.
• Immunized mice and measured NadA antibody levels and complement-mediated serum bactericidal activity.

Main Results:

• Both ferritin-NadA nanoparticle designs self-assembled as expected.
• Nanoparticles induced 10- to 100-fold higher NadA antibody levels compared to NadA trimers.
• Potent complement-mediated serum bactericidal activity was observed.

Conclusions:

• Self-assembling ferritin nanoparticles effectively enhance the immunogenicity of bacterial antigens like NadA.
• This approach is broadly applicable for vaccine development, particularly for trimeric antigens.
• Nanoparticle-based vaccines offer a promising strategy for combating bacterial infections.