| The first part:in the previous work,we prepared a mutant strain M3 with a significantly attenuated phenotype,which contained deletion mutations of three genes.Through the analysis of the biological characteristics and pathological infectivity of the mutant strain M3,it was found that the mutant strain had very low proliferation ability and weak pathogenicity compared with the wild type strain.At the same time,by establishing the evaluation and analysis of the infected animal model,the mutant strain M3 can induce the corresponding protective immune response.Although M3 initially stimulated the immune protection ability of mice,its protective effect was not enough to completely resist the invasion of the virus.Therefore,in order to continue to explore the research and development of preventive vaccine,the following work was done in this paper.Based on the mutant strain M3,we mutated the related sites of the corresponding genes,and constructed a new mutant strain named Ma.as the mutant strain Also,following the previous process of evaluating vaccine candidate strains,this paper will evaluate the biological characteristics,attenuated phenotypes and immune protection effects of mutant strain Ma.For the exploration of qualified HSV-1 vaccine candidate strains to provide a reference.Studies Ma mutant strains at the cell level showed that a combination of six genes combined with mutations produced a characteristic low proliferative type mice inoculated with mutant Ma showed no clinical symptoms.these data initially support the safety of mutant Ma as a candidate experimental vaccine.adaptive immune responses characterized by neutralizing antibodies and specific cellular immune responses were induced Ma mice inoculated with two mutant strains.If the wild strain is attacked,the immune response can effectively control the clinical symptoms of each group caused by virus infection,which preliminarily confirms the Ma immune protection.Further,the detection of virus load and histopathology in various tissues confirmed the control of virus infection and pathological damage caused by this immune response.Therefore,mutant strains Ma exhibit the immunogenicity and safety necessary for attenuated vaccines,and they can protect mice against HSV-1 attacks.On the basis of the mutant strain Ma,our research group mutated the related sites of the related genes,and constructed a new mutant strain named Mb.To test their biological properties,we found that Mb have lower proliferative properties,innate immune characteristics with up-regulated IFN-I signaling pathways,and potential to stimulate good adaptive immune responses.We also know more about the ICP34.5 of RL1 coding,may have different ability to regulate viral gene transcription in HSV-1 and HSV-2,Meanwhile,in this experiment ICP34.5 the effect on IFN-I signaling pathway was demonstrated again.The third part:we use the Meta analysis method to the global 1980?2018 published HSV-1 new infection and risk factors related research results summary and quantitative comprehensive analysis;Review Manager5.3 software was used for heterogeneity test,effect quantity combined statistical analysis,bias test and sensitivity analysis.Female(OR=1.33,95%CI:1.20?1.47%,P<0.001),aged over 40(ORP<2.99),95%CI?1.84?4.86%,P<0.001),low age at first sexual intercourse(ORP<1.22),95 per cent CI:1.09?1.36 per cent,P<0.001),lower level of education(ORP<1.68),95%CI:1.23?2.29%,P=0.001,low income(ORP=2.25,95 CI:1.38?3.66,P<0.001)is a risk factor for HSV-1 infection.Previous HSV-2(OR=0.96,95%CI:0.84?1.11,P>0.5)infection has no relationship with HSV-1 new infection.Accordingly,we should focus on strengthening the sexual knowledge of women,adolescents,the bottom of society and the publicity and education of viral infections,including HSV-1.According to the risk of infection HSV-1 of different ages,the vaccination plan of clinical trial of candidate vaccine can be formulated. |
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