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

Front Immunol. 2023 Jan 19:14:1088501. doi: 10.3389/fimmu.2023.1088501. eCollection 2023.

Abstract

Staphylococcus aureus infection is a severe public health concern with the growing number of multidrug-resistant strains. S. aureus 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 S. aureus 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 S. aureus click vaccine. We decorated OMVs with surface exposed SpyCatcher via a truncated OmpA(a.a 1-155)-SpyCatcher fusion. The engineered OMVs can flexibly bind with various SpyTag-fused S. aureus 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 S. aureus Newman lethal challenge in a mouse model. Our study provided a flexible and versatile click vaccine strategy with the potential for fighting against emerging S. aureus clinical isolates.

Keywords: SpyCatcher-SpyTag; Staphylococcus aureus vaccine; flexible antigen display; multi-targeting vaccine; outer membrane vesicles; ‘click’ display.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens
  • Bacterial Outer Membrane
  • Immunity, Cellular
  • Mice
  • Staphylococcal Infections* / prevention & control
  • Staphylococcus aureus
  • Vaccines*

Substances

  • Vaccines
  • Antigens

Grants and funding

The research was supported by the National Key Research and Development Program of China (2021YFA0910700, 2018YFA0902701), the Health and Medical Research Fund, the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region (COVID190117, COVID1903010, T-11-709/21-N) and Guangdong Science and Technology Department (2020B1212030004) to JH and the National Natural Science Foundation of China (Grant No. 82003259) to JS.