| Objective:To systematically evaluate the immune efficacy and safety of human H7N9 influenza virus vaccine and provide evidence-based medical evidence for the prevention of H7N9 avian influenza.Methods:Literature search of VIP,Wan fang,CBM,CNKI and EMBASE,Pubmed,Cochrane library were conducted Library up through January30,2019.All articles on the immunogenicity of H7N9 influenza vaccines in the healthy Adults were included.Two researchers independently searched the literature according to the established search terms and retrieval methods,screened the literature according to inclusion exclusion criteria,and evaluated the quality of the methodology based on the “Methodological Index for Nonrandomized Studies”.The main outcome indicators in this study were the level of specific antibodies after vaccination,including seroconversion rate(SCR)and geometric mean titer(GMT),and the secondary outcome indicators were adverse event rate(AES).Firstly,all the studies included were systematically evaluated,and the changes of SCR and GMT of different vaccines after immunization were analyzed.Second,Revman5.0 software was used for meta-analysis of the results of inactivated vaccine research.RR and 95% CI were used as combined effects.Stata14.0 software was used to merge SCR of the same dose group of inactivated vaccine and evaluate the safety of vaccine.Heterogeneity was tested by I~2 value and publication bias was analyzed by Egger and s test.Results:(1)10 English literatures were included with 3153 subjects.The geometric mean titer(GMT)and seroconversion rate(SCR)of serum specific antibodies of all types of H7N9 vaccines after 2 doses were higher than those of the first dose.6 studies on inactivated vaccines were included in the meta-analysis.After two doses of H7N9 non-adjuvant H7N9 vaccine,the SCR of antibody SCR increased(RR(95% CI):15?g: 3.39(1.89,6.08),30?g:2.35(1.25,4.40),45?g:3.80(1.45,9.99).when test by HI,the same dose of antibody SCR(95% CI)of 15?g,30?g and 45?g group were 10.1(4.0,16.2)?36.9(32.5,61.7)and 8.0(3.2,12.8);when test by MN,SCR were 12.6(6.6,18.6)? 38.8(25.2,53.8)and 20.1(14.4,25.7),respectively,which did not meet the vaccine licensing standards.In the adjuvant groups,after vaccination by two dose,the SCR was significantly higher than one dose,RR of 3.75?g:for AS03:8.85(3.78,20.72),MF59: 22.29(7.84,63.35);RR of 7.5?g:AS03:5.09(2.47,10.49),MF59:24.35(3.98,148.98);RR of 15?g:AS03:8.10(4.48,14.65),MF59:14.82(6.69,32.82),respectively.SCR of 3.75?g: AS03:89.1(84.8,93.3),MF59:42.0(9.6,74.4);7.5?g: AS03:87.2(75.7,98.6),MF59:50.9(36.7,65.1);15?g:AS03: 84.0(76.0,91.0),MF59:52.1(46.4,57.8).the RR of adjacent adjuvant vaccine groups,AS03:7.5?g VS 3.75?g: 0.98(0.91,1.05),15?g VS 7.5?g: 1.04(0.92,1.19),MF59 adjuvant vaccine: 7.5?g VS 3.75?g: 1.21(0.98,1.49),15?g VS 7.5?g: 0.97(0.80,1.18),respectively.In the 15?g oil-in-water adjuvant vaccine groups,when test by HI,the SCR(95% CI)of the first dose,the second dose and the second dose were 49%(20.9,77.2),23.7%(16.3,31.2)and 52.7%(36.2,69.2),respectively.SCR of two dose of adjuvant vaccine was higher than only one adjuvant vaccine(two doses adjuvant VS the first dose adjuvant: RR = 1.19(1.02,1.39);two doses adjuvant VS the second dose adjuvant: RR = 2.50(1.92,3.26).(2)Pain and erythema were the main local adverse reactions after vaccination.The incidence of pain in 3.75?g,7.5?g,15?g and 30?g adjuvant vaccines was 63%,79%,64%,84%;the incidence of erythema was 10%,12%,21% and 32% respectively.The incidence of pain and erythema in the 15?g and ?30?g non-adjuvant vaccines groups were 37% and 54%;16% and 22% respectively.The main adverse symptoms were fatigue,muscle pain and headache.In the adjuvant groups of 3.75?g,7.5?g,15?g and 30?g,the incidence of fatigue was 32%,38%,28%,48%;the incidence of muscle pain was 24%,32%,21%,48%,headache was 34%,37%,20%,18%,and in the no-adjuvant groups of 15?g and ?30?g,the incidence of fatigue was 25%,27%;muscle pain was 21%,25%;the incidence of headache was 22% and 21%,respectively.Conclusion:1.After a single dose of vaccination the SCR of all H7N9 influenza virus vaccines could not reach the license standards of CBER and CHMP vaccines.After strengthening the second dose of vaccination,the non-adjuvant vaccines still could not play an effective protectiverole,while the SCR of all oil-in-water adjuvant(AS03/MF59)vaccines met the standards.2.The adjuvant can significantly enhance the immune effect of H7N9 influenza virus vaccine.The oil-in-water adjuvant(AS03/MF59)can meet the vaccine licensing standard at a lower dose(3.75?g).3.The time point of the adjuvant used can affect the immune effect of the vaccine.The SCR of two dose adjuvants vaccine is significantly higher than only one dose add with adjuvant,and the SCR of the first dose is higher than that of the second dose.4.The inactivated H7N9 avian influenza virus vaccine is safe,and there are no serious adverse events related to vaccination.Although the incidence of local and systemic adverse events of adjuvant vaccines was slightly higher than that of non-adjuvant vaccines,the symptoms were mild and self-limiting. |
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