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@#Objective To evaluate the safety and efficacy of basic immunization with different sequential immunization programs of oral live attenuated poliomyelitis vaccine(OPV)and inactivated poliomyelitis vaccine(IPV). Methods Infants above two months of age residing in Pudong New Area,Shanghai,were selected for the study,and the basic immunization program of OPV full course(O-O-O group),sequential IPV and OPV(I-I-O group),and IPV full course(I-I-I group)were administered at 2,3 and 4 months of age,respectively. Relevant adverse reactions were proactively monitored by the parents of the participants via completing their own self-observation form after immunization. Before and after immunization,blood samples were collected from the upper arm vein,and the serum was separated. The neutralizing antibody levels of poliovirus in serum were measured by micro neutralization test,and the antibody positive rate and geometric mean titer(GMT)were calculated. Logistic multivariate regression analysis was used to research the effects of group,gender,household registration,birth mass and positive rate of typeⅠ/Ⅲ antibody before immunizationon the positive rate of type Ⅰ/Ⅲ antibody after basic immunization. Results There were one case of lethargy and one case of crying in O-O-O group, one case of lethargy in I-I-O group,and one case of crying in I-I-I group. The GMTs of type I neutralizing antibody in the pre-immunization O-O-O group,I-I-O group,and I-I-I group were 41. 39,8. 21,and 12. 56,and those of type Ⅲ neutralizing antibody were 7. 57,4. 02 and 8. 08,respectively. There was no significant difference in GMT between groups for typeⅠandⅢneutralizing antibodies before immunization(F = 2. 815 and 0. 608,P = 0. 061 and 0. 545,respectively). The positive rates of type Ⅰ antibody before immunization were 24. 04%,34. 07% and 41. 00%,respectively,with significant difference between groups(χ~2= 13. 459,P = 0. 001). The positive rates of type Ⅲ antibody were 13. 94%,9. 89% and 18. 00%,respectively,with no significant difference(χ~2= 5. 188,P = 0. 075). After immunization,the GMTs of type Ⅰ neutralizing antibody were 1 311. 84,1 812. 59 and 833. 24,and those of type Ⅲ neutralizing antibody were 911. 97,1 752. 68 and 419. 50,respectively,with significant differences between groups(F = 76. 848 and 202. 632,respectively,each P < 0. 001). After immunization,the positive conversion rates of type Ⅰantibody were 98. 56%,100% and 100%,and those of type Ⅲ antibody were 99. 04%,100% and 99. 44%,respectively,with no significant difference between the two groups(χ~2= 2. 973 and 1. 045,P = 0. 122 and 0. 789,respectively). In addition,group,gender,household registration,birth mass and positive rate of typeⅠ/Ⅲantibody before immunization had no effect on the positive conversion rate of typeⅠ/Ⅲantibody after basic immunization. Conclusion All three sequential immunization programs achieved good safety and high antibody positive conversion rates after basic immunization.
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Sequential immunization is one of the special means to solve the shortage of vaccines, respond to SARS-CoV-2 variants and improve the efficacy of vaccines in the current pandemic period. This article mainly reviewed five sequential immunization strategies using the vaccines authorized by World Health Organization: priming with inactivated vaccine and boosting with recombinant protein vaccine, vector vaccine or mRNA vaccine; priming with vector vaccine and boosting with mRNA vaccine; prime-boost immunization with mRNA vaccines produced by different manufactures. Results of the related studies showed that heterologous sequential immunization strategies were safe and effective, and higher immunogenicity and efficacy could be achieved by sequential immunization. In addition, sequential immunization could provide certain protective effects against SARS-CoV-2 variants.
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Objective To investigate whether a novel sequential immunization strategy was more superior to the traditional immunization strategy in eliciting immune responses by using domainⅢof dengue envelope proteins (EDⅢs) as immunogens. Methods EDⅢ subunit proteins of four serotypes of dengue viruses (DENVs) were expressed in a baculovirus expression system. SDS-PAGE and Western blot were performed to analyze the purity and specificity of purified recombinant proteins, respectively. In order to evaluate the immunogenicity of EDⅢ-based immunization strategies, female BALB/c mice were subcutane-ously immunized with PBS,tetravalent mixture of four EDⅢrecombinant proteins,or the four EDⅢproteins sequentially for four times with two weeks interval between each immunization. Two-week after the final im-munization,splenocytes were isolated and analyzed by ELISPOT assay to evaluate T cell responses and serum samples were collected for plaque reduction neutralization test(PRNT). Results Both immunization strate-gies of sequential EDⅢproteins and tetravalent EDⅢproteins could elicit stronger antigen-specific Th2(IL-4) cell responses in immunized mice than PBS did and the former was superior to the latter. Only the se-quential immunization strategy could induce Th2 cell responses in immunized mice against peptide segments of DENV2 EDⅢ. Tetravalent EDⅢ proteins performed better than the sequential immunization strategy in inducing higher levels of neutralizing antibodies against DENV-1,DENV-2 and DENV-3,while both immu-nization strategies failed to generate neutralizing antibodies against DENV-4. Conclusion Sequential immu-nization with DENV EDⅢ proteins induced stronger T cell responses, but weaker neutralizing antibody re-sponses against DENV than tetravalent EDⅢ proteins did.
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The aim of this study is to investigate the immune effects of BCG primary immunization and IL-12 combined with Mycobacterium tuberculosis Ag85A DNA vaccine booster immunization on mice .We randomly divided the mice into 7 groups ,namely PBS negative controls ,BCG controls ,pcAg85A controls ,BCG primary immunization combined with Ag85A booster immunization controls ,BCG primary immunization combined with Ag85A and IL-12 booster immunization controls , BCG primary immunization combined with IL-12 booster immunization controls ,and BCG primary immunization combined with pcDNA3 .1 booster immunization controls .Implementing the immune in procedure of BCG primary immunization and cytokine IL-12 booster immunization combined with mycobacterium tuberculosis Ag85A DNA ,we observed the immune effect on mice by detecting the mice serum total IgG , specific lymphocyte proliferation and cytokine levels in 4 ,6 ,8 weeks after the last immunization .Comparing the mice immunized in the strategy of BCG primary immunization and cytokine IL-12 combined with Mycobacterium tuberculosis Ag85A DNA vaccine strengthening immunization to the mice in other groups by other immune ways ,we found that ,in BCG/Ag85A+ IL-12 groups ,IgG in-creased significantly (P< 0 .05) ,specific lymphocyte prolifera-ted significantly ,and after strengthening immunization IFN-γlevels ,IL-2 levels and IL-4 levels in the three periods were 128 .2 ±20.4,190.2±16.51,244.2±39.14 ;146.2±17.29,271.6±16.36and16.36±28.12 ;68.6±6.62,96.6±5.5and5.5± 10 .71 ,respectively ,which were higher than those in other groups (P<0 .05) .It’s suggested that the immunization way of BCG primary immunization and cytokine IL-12 combined with Mycobacterium tuberculosis Ag85A DNA vaccine booster immu-nization could significantly enhance the humoral and cellular immunity of the bodies ,and provide the basis for further study on protective effect test in animals .
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Objective:To investigate the immune efficacy after sequential immunization with Mycobacterium tuberculosis DNA vaccine encoding mature form of Ag85B(pTB30m)and Mycobacterium tuberculosis H37Ra in mice.Methods:Much of highly pure plasmid DNA(pTB30m)extracted by alkaline lysis method was confirmed by restriction endonuclease digestion.Then,its DNA concentration and purity were determined by UV spectrophotometry.At various intervals(4weeks,8weeks)after sequential immunization,ELISA was used to detect the level of the serum antibody against PPD.Also,the spleen lymphocytes of mice were cultured with PPD in vitro.Lymphocyte transformation was detected by MTT assay.Results:Prepared pTB30m was highly pure and came to the needed concentration.Compared with Group Naive control,the specific antibody levels against PPD and the stimulation index(SI)of spleen lymphocytes were all statistically higher in Group DNA-85B/H37Ra(P0.05),as compared with Group DNA-85B/BCG,Group H37Ra and Group BCG,However,compared with Group H37Ra and Group BCG,the SI of mice was significantly larger in Group DNA-85B/H37Ra(P