Hydrogen peroxide-inactivated bacteria induces potent humoral and cellular immune responses and releases nucleic...

The problem of nosocomial infection is seriously escalating. Bacterial vaccines are indispensable for preventing infections caused by multi-drug resistant organisms. Some researchers have put forward the use of hydrogen peroxide (H₂O₂) as a new technology platform for virus deactivation. This deactivated virus can induce the number of CD8⁺ T lymphocytes, which can enhance antiviral responses. Although, H₂O₂ treatment has been rarely reported on the exploration of bacterial deactivation, H₂O₂ deactivation of whole-cell bacteria could be a potential novel approach for bacterial vaccine development. Here we present a strategy for H₂O₂-deactivated bacterial whole-cell vaccines, for two major pathgens, Pseudomonas aeruginosa and Staphylococcus aureus. The proactive effects of vaccination were assessed in vitro and in vivo. H₂O₂-deactivation of bacterial vaccines retains more complete epitopes and exhibits lower toxicity, as compared to formaldehyde, a conventional deactivator that was investigated in this study. Furthermore, H₂O₂-deactivated bacterial vaccines induce anti-infection responses through enhancement of humoral immunity and cellular immunity. Vaccination with H₂O₂-deactivated whole-cell bacteria in mice mainly elicits whole-cell specific antibody titers and balances the IgG2a and IgG1 response, predominantly with IgG3 induction at the later stages, meanwhile provides opsonic protection against challenge with pathogens. Finally, H₂O₂ deactivation of bacteria has been found to cause the release of bacterial DNA which is followed by NF-κB activation. These findings demonstrate that the deactivation of whole-cell bacteria with H₂O₂ is potentially advantageous for immune responses. Considering the prevention of drug-resistant infections, this deactivation method could be simultaneously applied as an innovative strategy for bacterial vaccine development.