Single-dose immunisation with a multimerised SARS-CoV-2 receptor binding domain (RBD) induces an enhanced and...

Area of Science:

• Biotechnology
• Vaccinology
• Structural Biology

Background:

• The COVID-19 pandemic, caused by SARS-CoV-2, necessitates effective vaccine strategies.
• Developing stable and potent vaccine formulations is crucial for global health security.

Purpose of the Study:

• To engineer stable, multivalent vaccine nanoparticles for SARS-CoV-2.
• To evaluate the immunogenicity and protective efficacy of these novel nanoparticles.

Main Methods:

• Utilized ferritin-like Dps protein from Sulfolobus islandicus as a scaffold.
• Employed the SpyCatcher system for covalent coupling of SARS-CoV-2 antigens (RBD) to Dps.
• Assessed nanoparticle stability, including after lyophilisation.
• Conducted immunisation experiments in mice and evaluated antibody titres, neutralising capacity, and in vivo protection against SARS-CoV-2 challenge.

Main Results:

• Successfully created stable, dodecameric vaccine nanoparticles (RBD-S-Dps) that remained intact post-lyophilisation.
• RBD-S-Dps elicited significantly higher antibody titres and enhanced neutralising antibody responses compared to monomeric RBD.
• A single dose of RBD-S-Dps provided complete protection against severe illness and led to viral clearance in SARS-CoV-2 infected mice.

Conclusions:

• Multimerised SARS-CoV-2 subunit vaccines, presented on ultra-stable scaffolds like Dps, represent a highly efficacious vaccine modality.
• The developed nanoparticle platform offers a promising approach for next-generation COVID-19 vaccines.