# A Modular Vaccine Platform Against SARS‐CoV‐2 Based on Self‐Assembled Protein Nanoparticles

## TL;DR

Researchers developed a modular vaccine platform using self-assembling nanoparticles to rapidly create vaccines against SARS-CoV-2 and its variants.

## Contribution

A modular vaccine platform using BP26 nanoparticles and SpyTag/SpyCatcher for site-specific antigen conjugation is introduced.

## Key findings

- BP26 nanoparticles with SARS-CoV-2 RBD elicited strong antibody responses in mice.
- The platform provides protection against lethal SARS-CoV-2 challenge in vivo.
- The system allows rapid adaptation to new viral variants through antigen exchange.

## Abstract

The COVID‐19 pandemic has underscored the urgent need for deployable vaccine platforms capable of rapidly responding to emerging and re‐emerging variants of human coronaviruses. BP26, an outer membrane protein of the zoonotic bacterium Brucella, self‐assembles into a highly ordered, barrel‐like nanoparticle that can serve as a vaccine platform, demonstrating immunogenicity against the influenza virus and cancer when combined with specific antigens. Here, we expanded its versatility by incorporating the SpyTag/SpyCatcher pair, enabling modular and site‐specific antigen conjugation via simple mixing. SpyCatcher was genetically fused to BP26, and SpyTag to the receptor binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) spike protein, generating RBD‐displaying BP26 nanoparticles (BP26‐RBD). Immunization of mice with BP26‐RBD elicited strong RBD‐specific and neutralizing antibody responses and conferred protection against lethal SARS‐CoV‐2 challenge. This plug‐and‐play nanoparticle design supports antigen production in diverse expression systems, retains antigenic structure, and allows multivalent display, providing a cost‐effective and rapidly adaptable strategy for next‐generation vaccines targeting evolving viral threats.

A modular BP26 nanoparticle vaccine platform incorporating the SpyTag/SpyCatcher system enables high‐density, repetitive antigen display with post‐expression flexibility. Conjugation of the SARS‐CoV‐2 RBD to BP26 nanoparticles elicits strong humoral immunity and confers protection against viral challenge in vivo. This plug‐and‐play system allows for rapid adaptation to emerging variants through facile antigen exchange, multivalent presentation, and compatibility with diverse expression systems.