Abstract
Although vaccines developed from live organisms have better efficacy than those developed from dead organisms, the mechanisms underlying this differential efficacy remain unexplored. In this study, we combined sub-immunoproteomics with immune challenge to investigate the action of the outer membrane proteome in the immune protection conferred by four Edwardsiella tarda whole-cell vaccines prepared via different treatments and to identify protective immunogens that play a key role in this immune protection. Thirteen spots representing five outer membrane proteins and one cytoplasmic protein were identified, and it was found that their abundance was altered in relation with the immune protective abilities of the four vaccines. Among these proteins, TolC and OmpA were found to be the key immunogens conferring the first and second highest degrees of protection, respectively. TolC was detected in the two effective vaccines (live and inactivated-30-F). The total antiserum and anti-OmpA titers were higher for the two effective vaccines than for the two ineffective vaccines (inactivated-80-F and inactivated-100). Further evidence demonstrated that the live and inactivated-30-F vaccines demonstrated stronger abilities to induce CD8+ and CD4+ T cell differentiation than the other two evaluated vaccines. Our results indicate that the outer membrane proteome changes dramatically following different treatments, which contributes to the effectiveness of whole-cell vaccines.
Highlights
Vaccines are the most effective strategy to control infectious diseases caused by pathogens[1,2]
Differential immune protection conferred by different vaccines that were derived from the same bacterium but prepared via different treatments has been observed[4,23], the mechanisms underlying this phenomenon are still unknown
We applied sub-immunoproteomics to investigate the relationship between differential outer membrane proteomes and immune protection by whole-cell bacterial vaccines prepared by different methods, as well as to identify key immunogens
Summary
Vaccines are the most effective strategy to control infectious diseases caused by pathogens[1,2]. The strong immune protection induced by live vaccines is attributed to the possibility that live vaccines may mimic natural infection, including secreted proteins, and naturally evoke the full immune response of the host[7,8] This hypothesis partly explains the differential immune protective abilities of different types of vaccines but does not provide answers regarding how inactivated vaccines derived from the same cells but treated via different methods lead to the induction of differential immune protection. We show that when E. tarda cells underwent differential treatment, the outer membrane proteome was significantly altered, including TolC, an immunogen that is key to mounting an effective immune response. These altered proteomes were found to be related to differential immune protective ability
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