Dual Plug-and-Display Synthetic Assembly Using Orthogonal Reactive Proteins for Twin Antigen Immunization

Area of Science:

• Biomolecular engineering
• Vaccine development
• Synthetic biology

Background:

• Modular platforms control biomolecular architecture for biological system manipulation.
• Current vaccines use single antigens; displaying multiple antigens on one particle is challenging for broader immunity.
• Icosahedral particles with single antigens are effective but limited in scope.

Purpose of the Study:

• To design a dually addressable synthetic nanoparticle platform for displaying multiple antigens.
• To overcome challenges in inducing broader immunity across strains or diseases.
• To accelerate vaccine development, particularly for malaria.

Main Methods:

• Engineered a nanoparticle using multimerizing coiled-coil IMX313 and two split proteins (SpyCatcher and SnoopCatcher).
• Utilized orthogonal protein ligation (SpyTag/SnoopTag) for spontaneous antigen attachment to opposite nanoparticle faces.
• Expressed the platform in Escherichia coli and tested its stability under various conditions.

Main Results:

• Demonstrated efficient derivatization with model proteins and pathogen-derived antigens.
• Confirmed the nanoparticle's resilience to lyophilization and extreme temperatures.
• Showed enhanced antibody response to malaria transmission-blocking antigens (Pfs25, Pfs28) when multimerized on the platform compared to monomers.

Conclusions:

• The SpyCatcher-IMX-SnoopCatcher platform offers a modular "plug-and-display" system for multivalent vaccines.
• This dual architecture facilitates the simultaneous display of multiple antigens, boosting immune responses.
• The platform shows promise for accelerating vaccine development for malaria and other infectious diseases.