Study On Immune Response Mechanism Of Enterovirus 71 Vaccine

Now the mechanism of most vaccines is unknown, so the development of newvaccines still remains in “experience” phase, resulting in a long-time and high-costvaccine development. In recent years, the concept of system vaccinology has beenproposed, which opens up a new school of thought for vaccine development. Enterovirus71vaccine is a new vaccine independently developed in China. Now three manufacturersin mainland have completed the phase III clinical trials, and the results showed that thevaccine had a good safety and protective effect.The protection rate against HFMD causedby EV71infection was more than90%, and against EV71infection-related diseases wasmore than80%. EV71vaccine is a novel vaccine, so it is significant to explore themechanism of EV71vaccine for accelerating vaccine development process. The purposeof this study is to explore the mechanism of EV71vaccine and to provide a theoreticalbasis for the development and application of EV71vaccine.In order to investigate the common mechanism of vaccine immune response, weused Meta-analysis to analyze the microarray expression profile data downloaded fromdatabase of NCBI GEO and ArrayExpress.We explored the common genes and pathwaysat the transcriptional level of innate and acquired immune response, and used RT-PCRwith EV71vaccine crowd to verify. The results showed that type I IFN genes andpathways were common in vaccine innate immunity, and the genes of EEF1A1and IL-18and the pathways of B and T cell receptor signaling activation pathway were common invaccine acquired immunity.In the second part, on the basis of Meta analysis, we used the microarray and proteinchip to explore the mechanism of EV71vaccine and obtained the transcriptome andproteomic spectra, in order to further reveal immune mechanism of EV71vaccine. Theresult of innate immune transcriptome analysis showed that type I IFN signaling pathwayplayed an important role in the innate immune response of EV71vaccine.We furthervalidated the research through animal and TLR4-deficient mice experiments.The resultsuggested that there may be a regulation pathway about TLR4→IRF9→IFN-I→Jak-STAT→immune cell activation.Through the correlation analysis of gene andneutralizing antibodies,we obtained that ELL2had the highest pearson correlation,which suggested that ELL2may be used as a biomarker for predicting the neutralizingantibodies.The result of adaptive immune transcriptome analysis showed that thefunction of DEG involved in cytokine-cytokine receptor interaction, cell adhesion andantigen processing and presentation, and so on. Through the correlation analysis of gene and neutralizing antibodies, we obtained that MX1and MX2had the highest pearsoncorrelation, which suggested that MX1and MX2may be used as biomarkers forpredicting the persistent immune response. The results of RT-PCR showed thatmicroarray result was reliable. By protein chip, we obtained the proteomic spectrum ofEV71vaccine adaptive immune response. The results showed that up-regulated geneswere mainly inflammatory proteins, chemokines, interferon-related proteins and celladhesion molecules and down-regulated genes were mainly immune regulationmolecules and pro-inflammatory factors. Through the correlation analysis of protein andneutralizing antibodies, we found that ICAM-1and IP-10respectively had a high pearsoncorrelation, which suggested that they may be used as markers for predicting the theneutralizing antibodies and the persistent immune response.Through Meta analysis, we got the common mechanism of vaccine innate andadaptive immune response. Through designed crowd and animal experiment, we explorethe transcriptome and proteomic spectra. This subject laid a good foundation for furtherexpounding the mechanism of EV71vaccine and screening the biomarker for predictingimmunogenicity of EV71vaccine.