Adenovirus Nanoparticles Displaying RBD Induce a Protective Immune Response Against BA.5 in Mice

Area of Science:

• * Vaccinology and Viral Vector Technology
• * Immunology and Infectious Diseases

Background:

• * Adenovirus (Ad) vectors are effective vaccine carriers, with hexon protein's hypervariable regions (HVRs) utilized for antigen display.
• * The COVID-19 pandemic highlighted the need for advanced vaccine platforms.

Purpose of the Study:

• * To develop a universal nanoparticle vaccine platform using recombinant Adenovirus (Ad) vectors.
• * To create a novel vaccine candidate, rAd3/7-SpyRBD, targeting SARS-CoV-2 BA5.2 strain.

Main Methods:

• * SpyCatcher/SpyTag technology was employed to incorporate SpyTag into hexon HVRs of rAd3/7.
• * Recombinant Adenovirus (Ad) vector rAd3/7-SpyTag was conjugated with SpyCatcher-fused SARS-CoV-2 receptor-binding domain (RBD).
• * Characterization involved Western blot, ELISA, TEM, particle size analysis, and mouse immunization studies.

Main Results:

• * A universal nanoparticle vaccine platform, rAd3/7-SpyTag, was successfully established with RBD displayed on its surface.
• * The rAd3/7-SpyRBD vaccine candidate demonstrated rapid induction of potent antibody responses and stronger immunity compared to SpyCatcher-RBD alone.
• * Both vaccine candidates provided protective immunity against the BA.5 strain in mice and induced neutralizing antibodies against Ad3 and Ad7.

Conclusions:

• * A trivalent vaccine candidate, rAd3/7-SpyRBD, was developed using a universal nanoparticle platform for immunity against SARS-CoV-2, Ad3, and Ad7.
• * This represents the first application of SpyCatcher/SpyTag technology in a bivalent rAd3/7 vector for achieving trivalent immunity.