AUTHOR=Sun Jingjing , Lin Xuansheng , He Yige , Zhang Baozhong , Zhou Nan , Huang Jian-dong 

TITLE=A bacterial outer membrane vesicle-based click vaccine elicits potent immune response against Staphylococcus aureus in mice

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1088501

DOI=10.3389/fimmu.2023.1088501

ISSN=1664-3224

ABSTRACT=<p><italic>Staphylococcus aureus</italic> infection is a severe public health concern with the growing number of multidrug-resistant strains. <italic>S. aureus</italic> can circumvent the defense mechanisms of host immunity with the aid of multiple virulence factors. An efficacious multicomponent vaccine targeting diverse immune evasion strategies developed by <italic>S. aureus</italic> is thus crucial for its infection control. In this study, we exploited the SpyCatcher-SpyTag system to engineer bacterial outer membrane vesicles (OMVs) for the development of a multitargeting <italic>S. aureus</italic> click vaccine. We decorated OMVs with surface exposed SpyCatcher <italic>via</italic> a truncated OmpA(a.a 1-155)-SpyCatcher fusion. The engineered OMVs can flexibly bind with various SpyTag-fused <italic>S. aureus</italic> antigens to generate an OMV-based click vaccine. Compared with antigens mixed with alum adjuvant, the click vaccine simultaneously induced more potent antigen-specific humoral and Th1-based cellular immune response, which afforded protection against <italic>S. aureus</italic> Newman lethal challenge in a mouse model. Our study provided a flexible and versatile click vaccine strategy with the potential for fighting against emerging <italic>S. aureus</italic> clinical isolates.</p>