Effects of age and influenza virus exposure on the cross-reaction of post-immune serum with H3N2 subtype mutants
-
摘要:
目的 评估年龄和既往流感病毒暴露史对免后血清与H3N2亚型变异株交叉反应的影响。 方法 将750名受试者按照1:1的比例接种试验用流感病毒亚单位疫苗和对照用流感病毒裂解疫苗，并且根据年龄和流感病毒暴露史分组，通过血凝抑制（hemagglutination inhibition，HI）试验测得受试者免疫前后血清针对疫苗株的血凝抑制滴度，与免疫后血清针对当年流行的4株H3N2亚型变异流感毒株的抗体滴度，计算抗体几何平均滴度（geometric mean titer，GMT），以及变异株和疫苗株的抗体GMT比值比，使用Kruskal-Wallis秩和检验比较不同年龄组以及不同既往流感暴露组之间的GMT比值比差异。 结果 在接种流感病毒亚单位疫苗的人群中，在免疫前同时暴露于H1亚型和B型流感病毒株的受试者，其针对A/Jiangsu-Nanchang/11926/2014（H3N2）的免后抗体水平高于无H1/B暴露的人群（t=3.913，P=0.001）。在接种流感病毒裂解疫苗的人群中，19~59岁的成年人针对A/Jiangsu-Haizhou/11044/2015（H3N2）免后交叉反应水平高于3~18岁的青少年（t=3.198，P=0.008）。 结论 先前暴露于H1亚型或B型流感病毒，可能会不同程度地影响H3免后抗体应答的交叉反应性，并因此可能影响疫苗效力。人类的免疫后反应存在年龄特异性差异。 Abstract:Objective To evaluate the effect of age and previous influenza exposure history on the cross-reaction of post-immune serum with H3N2 subtype mutants. Methods 750 subjects were vaccinated with the test influenza virus subunit vaccine and the control influenza virus split vaccine at a ratio of 1:1, and were grouped according to age and influenza virus exposure history. Through the hemagglutination inhibition(HI)test, the serum hemagglutination inhibition titer of the subject before and after immunization against the vaccine strain, and the antibody titer of the immunized serum against the four H3N2 subtype variant influenza strains that were circulating in that year were measured. Calculate the geometric mean antibody titer(GMT)and the ratio of the antibody GMT ratio between the variant strain and the vaccine strain. The Kruskal-Wallis rank sum test was used to compare the difference in GMT odds ratio between different age groups and between different previous influenza exposure groups. Results In the population vaccinated with influenza virus subunit vaccine, subjects exposed to both H1 subtype and B lineage virus strains before immunization had higher post-immunization antibody levels against A/Jiangsu-Nanchang/11926/2014(H3N2)than those without exposed to H1/B (t=3.913, P=0.001). Among the people vaccinated with influenza virus split vaccine, adults aged 19-59 years faced A/Jiangsu-Haizhou/11044/2015 (H3N2)post-immunization cross-reactivity levels higher than those aged 3-18 years (t=3.198, P=0.008). Conclusions Previous exposure to H1 subtype or B lineage influenza viruses may affect the cross-reactivity of antibody responses after H3 immunity to varying degrees, and therefore may affect vaccine efficacy. There are age-specific differences in human post-immunization responses. -
Key words:
- Influenza virus /
- Influenza vaccine /
- Exposure history /
- Cross-reaction
-
图 1 不同免前暴露的受试者对H3N2亚型流感疫苗株与变异株的抗体GMT水平比较
注:* *表示两组间差异存在统计学意义
Figure 1. Comparison of antibody GMT levels of H3N2 subtype influenza vaccine strains and mutant strains in subjects with different pre-immunization exposures
表 1 各年龄层受试者对流感病毒H3N2亚型疫苗株和变异株的GMT及GMT比值比
Table 1. GMT and GMT ratios of antibodies against influenza virus H3N2 subtype vaccine strains and mutant strains by subjects of all agesstrains
分组 H3N2毒株 6~36月 3~岁 19~岁 ≥60岁 H值 P值 GMT GMT比(%) GMT GMT比(%) GMT GMT比(%) GMT GMT比(%) 试验组 A/Jiangsu Nanchang/11926/2014 51.09 24.33 84.56 44.75 137.92 64.05 160.00 65.98 9.69 0.021 A/Jiangsu Qixia/31/2015 94.17 44.85 102.67 54.34 102.47 47.59 160.00 65.98 1.17 0.761 A/Jiangsu Quanshan/1234/2015 109.36 52.08 108.53 57.43 118.88 55.21 183.79 75.79 0.62 0.891 A/Jiangsu Haizhou/11044/2015 123.59 58.86 114.72 60.71 215.34 100.00 183.79 75.79 3.71 0.294 A/Texas/50/2012(疫苗株) 209.98 100.00 188.96 100.00 215.34 100.00 242.51 100.00 对照组 A/Jiangsu Nanchang/11926/2014 66.62 33.77 160.00 43.32 115.22 100.00 131.25 37.15 7.24 0.065 A/Jiangsu Qixia/31/2015 126.44 64.10 123.01 33.31 64.27 55.78 118.88 33.65 5.47 0.140 A/Jiangsu Quanshan/1234/2015 113.88 57.74 145.41 39.37 80.00 69.43 131.25 37.15 3.85 0.279 A/Jiangsu Haizhou/11044/2015 131.50 66.67 198.40 53.72 148.74 129.09 144.92 41.02 10.75 0.013a A/Victoria/210/2009(疫苗株) 197.24 100.00 369.34 100.00 115.22 100.00 353.31 100.00 注：aP＜0.05表示各年龄层受试者在针对此流感变异株与疫苗株的GMT比值比存在统计学差异。 
下载: 导出CSV
表 2 不同免前暴露的受试者对H3N2亚型流感疫苗株和变异株的抗体GMT和GMT比值比
Table 2. GMT and GMT ratio of antibodies against H3N2 subtype influenza vaccine strains and mutant strains in subjects with different pre-immunization exposures
分组 H3N2毒株 H1/B免前阴性 H1免前阳性 B免前阳性 H1/B免前阳性 H值 P值a GMT GMT比(%) GMT GMT比(%) GMT GMT比(%) GMT GMT比(%) 试验组 A/Jiangsu Nanchang/11926/2014 71.71 34.72 146.72 46.88 181.41 66.21 212.46 74.81 17.29 ＜0.001 A/Jiangsu Qixia/31/2015 100.30 48.56 120.73 38.57 136.24 49.72 151.18 53.23 1.06 0.790 A/Jiangsu Quanshan/1234/2015 113.55 54.86 167.08 53.38 146.17 53.35 154.06 54.25 0.14 0.990 A/Jiangsu Haizhou/11044/2015 134.30 64.88 186.20 59.49 210.91 76.97 217.88 76.72 1.36 0.710 A/Texas/50/2012(疫苗株) 206.55 100.00 313.14 100.00 273.86 100.00 283.89 100.00 对照组 A/Jiangsu Nanchang/11926/2014 93.00 43.66 131.55 73.90 169.81 70.17 144.03 64.88 5.30 0.150 A/Jiangsu Qixia/31/2015 106.96 50.22 94.00 52.81 126.35 52.21 108.71 48.97 0.74 0.860 A/Jiangsu Quanshan/1234/2015 111.54 52.37 151.06 84.87 148.42 61.33 139.73 62.94 4.16 0.240 A/Jiangsu Haizhou/11044/2015 146.07 68.58 158.92 89.28 189.96 78.50 176.96 79.71 2.69 0.440 A/Victoria/210/2009(疫苗株) 213.01 100.00 177.72 100.00 241.77 100.00 222.43 100.00 注：aP＜0.05表示各年龄层受试者在针对此流感变异株与疫苗株的GMT比值比存在统计学差异。
下载: 导出CSV
-
[1] Fonville JM, Wilks SH, James SL, et al. Antibody landscapes after influenza virus infection or vaccination[J]. Science, 2014, 346(6212):996-1000. DOI: 10.1126/science.1256427. [2] Carlock MA, Ingram JG, Clutter EF, et al. Impact of age and pre-existing immunity on the induction of human antibody responses against influenza B viruses [J]. Hum Vaccin Immunother, 2018,15(9):2030-2043. DOI: 10.1080/21645515.2019.1642056. [3] Castilla J, Navascués A, Fernández-Alonso M, et al. Effectiveness of subunit influenza vaccination in the 2014-2015 season and residual effect of split vaccination in previous seasons [J]. Vaccine, 2016,11(34):1350-1357. DOI: 10.1016/j.vaccine.2016.01.054. [4] Olafsdottir TA, Alexandersson KF, Sveinbjornsson G, et al. Age and influenza-specific pre-vaccination antibodies strongly affect influenza vaccine responses in the icelandic population whereas disease and medication have small effects [J]. Front Immunol, 2018,8:1872. DOI: 10.3389/fimmu.2017.01872. [5] Ross TM, Lin CJ, Nowalk MP, et al. Influence of pre-existing hemagglutination inhibition titers against historical influenza strains on antibody response to inactivated trivalent influenza vaccinein adults 50-80 years of age [J]. Hum Vaccin Immunother, 2014,10(5):1195-1203. DOI: 10.4161/hv.28313. [6] Lee J, Boutz DR, Chromikova V, et al. Molecular-level analysis of the serum antibody repertoire in young adults before and after seasonal influenza vaccination [J]. Nat Med, 2016,22(12):1456-1464. DOI: 10.1038/nm.4224. [7] Xie H, Li L, Ye Z, et al. Differential effects of prior influenza exposures on H3N2 cross-reactivity of human post-vaccination sera [J]. Clin Infect Dis, 2017,65(2):259-267. DOI: 10.1093/cid/cix269. [8] Taubenberger JK, Kash JC. Influenza virus evolution, host adaptation, and pandemic formation [J]. Cell Host Microbe, 2010,7(6):440-451. DOI: 10.1016/j.chom.2010.05.009. -
点击查看大图
图(1) / 表(2)
计量
- 文章访问数: 231
- HTML全文浏览量: 142
- PDF下载量: 37
- 被引次数: 0