Design of a mutation-integrated trimeric RBD with broad protection against SARS-CoV-2

Area of Science:

• Virology
• Immunology
• Vaccine Development

Background:

• Emerging SARS-CoV-2 variants necessitate vaccines with broad protective capabilities.
• Immune escape and evolutionary convergence are key factors in variant selection.

Purpose of the Study:

• To develop a broadly protective vaccine candidate against SARS-CoV-2 variants.
• To combine heterologous receptor-binding domains (RBDs) and immune-escape hotspots into a single immunogen.

Main Methods:

• Selection of representative SARS-CoV-2 strains based on immune-escape and evolutionary convergence.
• Structural and computational analyses to design a mutation-integrated trimeric RBD (mutI-tri-RBD).
• Comparison with a homologous trimeric RBD (homo-tri-RBD) vaccine candidate.

Main Results:

• mutI-tri-RBD induced significantly higher neutralizing antibody titers against Delta and Beta variants compared to homo-tri-RBD.
• mutI-tri-RBD demonstrated broad neutralizing activity against 23 SARS-CoV-2 variants in pseudovirus assays.
• In vivo studies in hACE2-transgenic mice showed potent protection against prototype, Delta, and Beta strains.

Conclusions:

• The mutation-integrated trimeric RBD (mutI-tri-RBD) is a promising vaccine candidate for broad SARS-CoV-2 protection.
• This strategy effectively addresses immune escape and provides robust protection against diverse variants.