流感防控 : 移动的盾或是盾墙 徐建青 上海市公共卫生临床中心 复旦大学生物医学研究院
汇报提纲 : 当前流感的防控模式 : 移动的盾对付移动的剑 流感防控的理想模式 : 构建有效的盾墙
汇报提纲 : 当前流感的防控模式 : 移动的盾对付移动的剑 流感防控的理想模式 : 构建有效的盾墙
冬有雪
春有百花
矛与盾的游戏 : 移动的盾对付移动的剑
一次疫苗接种 对宿主 流感抗体屏障 的影响
单一流感疫苗接种 : 一对一的游戏吗? inhibition (%) 00 80 60 0 0 0-0 -0 :50 :00 :00 T09 H :00 :800 :600 serum dilution :00 Mock T09 H :600 :800 inhibition (%) 00 Mock T09 H 80 60 0 0 0-0 :50 :00 :00 R07 H :00 :800 serum dilution :600 :00 :600 inhibition (%) :50 :00 :00 SI86 H 00 Mock 80 T09 H 60 0 0 0-0 -0 :00 :800 serum dilution :600 :00 :600 J57 H MO99 H VN0 H5 inhibition (%) 00 Mock T09 H 80 60 0 0 0-0 :50 :00 :00 :00 :800 serum dilution :600 :00 :600 inhibition (%) 00 Mock 80 T09 H 60 0 0 0-0 -0 :50 :00 :00 :00 :800 serum dilution :600 :00 :600 inhibition (%) 00 Mock 80 T09 H 60 0 0 0-0 -0 :50 :00 :00 :00 :800 serum dilution :600 :00 :600 Qiu, et al. lin Infect is, 0
成年人 一次疫苗 免疫前后 HI 抗体滴度 I Year of birth Gender HI titer Pre-vaccination Post-vaccination 95 female 0 0 0 955 female 0 80 960 male 0 60 8 96 female 0 80 965 male 0 60 0 968 female 0 60 6 969 female 0 80 0 97 female 0 60 975 female 5 0 8 976 female 5 80 5 977 female 0 80 5 977 male 0 60 0 979 female 0 0 979 female 5 0 9 98 female 5 0 0 98 female 80 0 7 98 male 5 0 9 98 female 0 0 98 female 5 60 9 98 male 0 80 9 987 female 0 60 5 989 female 0 0 989 male 5 0
5 9 9 9 7 0 9 0 5 5 8 0 6 0 8 0 Homologous immune responses in sera of 009 pandemic vaccine recipients a) b) c) I50 titer (log) 6 8 0 6 8 I50 Titer (log) 7 6 5 0 9 8 5 6 7 8 9 0 HI titer (log) I50 7 5 9 7 5 7 9 HI
ross-reactive neutralization activities to heterosubtypes of influenza viruses in sera of 009 pandemic vaccine recipients. Fig. c) d) /Japan/05/57(HN) /Viet Nam/0/00(H5N) 5 9 9 7 5 8 6 0 8 0 5 9 9 9 7 0 9 0 5 5 8 0 6 0 8 0 6 8 0 I50 titer (log) 6 8 0 I50 Titer (log) 9 7 5 6 8 0 HI titer (log) 9 7 5 R=0.59 P=0.009 R= -0.8 P=0.506 6 8 0 HI titer (log) I50 (log) I50 (log) 0 8 6 5 7 9 9 7 5 R=0.698 P=0.009 HI (log) 5 7 9 HI (log) Qiu, et al. lin Infect is, 0
ross-reactive neutralization activities to heterosubtypes of Fig. influenza viruses in sera of 009 pandemic vaccine recipients. /Moscow/0/999(HN) a) 5 9 9 9 7 0 0 5 5 8 0 6 0 8 0 8 0 6 8 8 6 R=0.85 P<0.000 0 8 6 8 0 HI titer (log) I50 (log) 7 5 R=0.70 P=0.0 9 5 7 9 HI (log) b) /risbane/59/007(hn) 5 9 9 0 0 8 7 8 9 0 I50 Titer (log) R=0.7 P=0.77 0 9 8 7 6 8 0 HI titer (log) 0 9 8 6 8 0 I50 Titers (Log) HI titers (Log) HI (Log)
IgG depletion completely abolish the crossreactive neutralizing antibodies T09 H I IgG+ IgG- 5 805 5 8 805 05 805 05 6 5 5 VN0 H5 I IgG+ IgG- 5 0 <0 8 80 <0 50 <0 6 50 <0 Qiu, et al. lin Infect is, 0
一次感染 对宿主 流感抗体屏障 的影响
Neutralization activities are mediated by IgG Huang Y. et al. unpublished data
ross-reactive to other H7 Neutralization activities Huang Y. et al. unpublished data
ross-reactive to other H Neutralization activities Huang Y. et al. unpublished data
onclusion:
汇报提纲 : 当前流感的防控模式 : 移动的盾对付移动的剑 流感防控的理想模式 : 构建有效的盾墙
家长的理想 : 样样都行
H 共享序列 (ON H) 免疫应答 H5
共享序列 on H 免疫后中和抗体应答
Schedule for animal immunization:
抗不同 H 中和抗体 T09 H *** *** *** *** nb titer (log) SI06 H nb titer (log) N99 H 5 nb titer (log) SI86 H nb titer (log) R07 H nb titer (log)
Schedule for animal immunization:
共享 + 序贯免疫 T09 H *** *** *** *** nb titer (log) SI06 H nb titer (log) N99 H 5 nb titer (log) SI86 H nb titer (log) R07 H nb titer (log) FJ0 H nb titer (log) R07 H nb titer (log) WI05 H 5 6 nb titer (log) MO99 H nb titer (log) J57 H nb titer (log) VN0 H5 nb titer (log) NL0 H7 nb titer (log) HK99 H9 nb titer (log) FI06 H *** *** nb titer (log) R08 H *** *** *** ** nb titer (log)
共享 + 序贯免疫动物实验 动物实验免疫分组与规划 组别 (n=5) (n=6) 第 0 周第 周第 8 周第 周 免疫原剂量免疫原剂量免疫原剂量免疫原剂量 pvk.0 00µg pvk.0 00µg pvk.0 00µg pvk.0 00µg pvk.0-r08 H 00µg pvk.0-on H 00µg pvk.0-on H 00µg pvk.0-on H5 00µg (n=6) pvk.0-r08 H 00µg pvk.0-on H 50µg pvk.0-on HG 50µg pvk.0-on H 00µg pvk.0-on H5 00µg 最后一针免疫完成后第 周处死小鼠, 进行评价
共享 + 序贯免疫
onclusion:
High level of conservation for H7N9 TL peptides. Sergio Quiñones-Parra et al. PNS 0;:09-05 0 by National cademy of Sciences
TL responses to conserved immunodominant H7N9 peptides. Sergio Quiñones-Parra et al. PNS 0;:09-05 0 by National cademy of Sciences
Rapid recovery from H7N9 infection driven by 8+ T-cell responses Wang Z, et al. Nat ommun, 05 Wang Z, et al. Nat ommun, 05
结论 具有广谱保护作用的 TL 在人群中存在较普遍 ; 流感特异性 TL 驱动患者的康复, 是主要保护力量 ; 通用型流感疫苗是可以研制出来的
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