⿃インフルエンザの疫学について - mhlw...cats aquatic mammals •h1 -h16 •n1 -n9...
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⿃インフルエンザの疫学について
国⽴感染研インフルエンザウイルス研究センターWHOインフルエンザ協⼒センター
センター⻑ ⼩⽥切孝⼈
1
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Influenza A VirusesAll influenza A virus subtypes are detected in aquatic birds
Aquatic birds
Dogs
Humans Pigs HorsesPoultry
Cats
Aquaticmammals
• H1 - H16• N1 - N9
Pandemic potential routes
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Zoonotic Influenza A viruses currently detected in Animals and Humans in the World (since Sept 2016)
Avian virusesH5Nx :
H5N1 (poultry, wild birds, human(6))(860)H5N2 (poultry, wild birds)H5N5 (wild birds)H5N6 (poultry, wild birds, human (16))H5N8 (poultry, wild birds)
H7N9 : (poultry, human(758), environment) (1564)H7N2 : (poultry)H9N2 : (environment, human(4))
Swine virusesH1N1v (pig)H1N2v (human(2), pig)H3N2v (human(31), pig)
http://www.who.int/influenza/vaccines/virus/201709_zoonotic_vaccinevirusupdate.pdf?ua=1
Since 2003,
Since 2013,
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Zoonotic Influenza A viruses currently detected in Animals and Humans in the World (since Sept 2016)
Avian virusesH5Nx :
H5N1 (poultry, wild birds, human(6))(860)H5N2 (poultry , wild birds)H5N5 (wild birds)H5N6 (poultry, wild birds, human (16))H5N8 (poultry, wild birds)
H7N9 : (poultry, human(758), environment) (1564)H7N2 : (poultry)H9N2 : (environment, human(4))
Swine virusesH1N1v (pig)H1N2v (human(2), pig)H3N2v (human(31), pig)
Since 2003,
Since 2013,
http://www.who.int/influenza/vaccines/virus/201709_zoonotic_vaccinevirusupdate.pdf?ua=1
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Evolution of A(H5) HA genes
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A(H5) activity birds
Mar Apr May Jun Jul Aug Sep
2.3.2.1c
2.2.1.2 2.3.2.1a
2.3.2.1c
2.3.4.4
Non GS/GD
2.3.2.1c
Global distribution of H5Nx virus clades
WHO VCM for 2018 Southern H, Sept 28 Melbourne
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A(H5) activity - birds since 27 September 2016
2.2.1.2
2.3.2.1a
2.3.2.1c
2.3.4.4
2.3.2.1c
WHO VCM for 2017-2018 Northern H, Mar 2 Geneva
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http://www.who.int/influenza/human_animal_interface/2017_07_25_tableH5N1.pdf?ua=1
Fatality rate = 53%
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Recent human infection cases with A(H5Nx) viruses
4 new reported cases,
860 A(H5N1) cases/453 fatal16 A(H5N6) cases/11 fatal
Sept. 2016~Feb. 2017
Mar. ~Sept. 2017
2 new A(H5N1) cases
Sept Oct Nov Dec Jan Feb
China Egypt
Mar Apr May Jun Jul Aug Sept
Egypt Indonesia
WHO VCM for 2017-2018 Northern H, Fen Mar 2 GenevaWHO VCM for 2018 Southern H, Sept 28 Melbourne
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WHO GISRS networkワクチン候補野生株の入手
感染研GMP facilityでワクチン製造株の作製
動物への感染等で安全性試験品質試験確認試験
無償配布
RG法で弱毒化したワクチン高増殖株の開発
国内外のワクチン製造所研究機関
厚労省のインフルエンザウイルス系統保存事業
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WHO-new CVV
New CVV of A/H5N6 (cl 2.3.4.4) from zoonotic virus library in NIID is available for distribution
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Available H5Nx CVVs provided by WHO CCs/ERLs
http://www.who.int/influenza/vaccines/virus/201703_zoonotic_vaccinevirusupdate.pdf?ua=1
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Zoonotic Influenza A viruses currently detected in Animals and Humans in the World (since Sept 2016)
Avian virusesH5Nx :
H5N1 (poultry, wild birds, human(9))(859)H5N2 (poultry , wild birds)H5N5 (wild birds)H5N6 (poultry, wild birds, human (4))H5N8 (poultry, wild birds)
H7N9 : (poultry, human(758), environment) (1564)
H7N2 : (poultry)H9N2 : (environment, human(9))
Swine virusesH1N1v (pig)H1N2v (human(5), pig)H3N2v (human(18), pig)
Since 2003,
Since 2013,
http://www.who.int/influenza/vaccines/virus/201709_zoonotic_vaccinevirusupdate.pdf?ua=1
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Data provided by China CDC
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Phylogenetic relationships of H7N9 virus HA genes
Data provided by China CDC
Pearl River Delta33 Genotypes
Yangtze River Delta36 Genotypes
JS537AnH1JS18828JX9530JS1SH7AnH1887……
GD2GD1GD8423DG397GX8970……
Other Region13 Genotypes
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Data provided by China CDC
Pandemic potential with H7N9 viruses is not low
Sustained H-to-H transmission is limited so far
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HPAI-H7N9 viruses emerged in 2017 and cocirculated with LPAI-H7N9 viruses in China
758 human cases of A(H7N9) virus infection (288 fatal) in 5th W Total cases since 2013 = 1564 with 610 deaths (fatality rate = 39%) Since 2017 HPAI-H7N9 viruses were detected in poultry and
in 28 human cases (14 fatal) Most of LPAI- and HPAI-H7N9 viruses are susceptible to antiviral of NAIs
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HPAI-H7N9 isolated from humans
HPAI-H7N9 isolated from chickens
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Available H7N9 CVVs provided by WHO CCs/ERLs
Yangtze river delta-lineage viruses (predominant-lineage)
High-path virusLow-path virus
http://www.who.int/influenza/vaccines/virus/201709_zoonotic_vaccinevirusupdate.pdf?ua=1
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H1N1pdm09 Trivalent seasonal
H7N9
84%
Seroconv
ersion
Split vaccine, Two doses(15 g@)
85% 81%
H7N9+MF59
0%
20%
40%
60%
80%
100%
H7N9 VLPISCOMATRIX
Two doses(5 g@)
89%
6%
H7N9 vaccine is low immunogenic in humans
Griffin MR et al. PLosOne (2011)Goodwin et al. MMWR (2013)http://www.Novartis.comNEJM (2014)
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Comparison of T cell epitope score among influenza vaccines
EpiMatrix protein score by immunoinformatic analysis:
Above zero: higher potential for immunogenicityBlow zero: lower potential for immunogenicity
+18.22
+14.30
DeGroot AS et al. (2013) Human Vaccines& Immunotherapeutics 9: 5
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H1N1pdm09 Trivalent seasonal
H7N9
84%Se
roconv
ersion
Split vaccine, Two doses(15 g@)
85% 81%
H7N9+MF59
0%
20%
40%
60%
80%
100%
H7N9 VLPISCOMATRIX
Two doses(5 g@)
89%
6%
Immunogenicity of H7N9 vaccine can be improved by adding suitable adjuvants
Griffin MR et al. PLosOne (2011)Goodwin et al. MMWR (2013)http://www.Novartis.comNEJM (2014)
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JAMA. 2015;314(3):237-246.
Effect of Varying Doses of a Monovalent H7N9 Influenza Vaccine With and Without AS03 and MF59 Adjuvants on
Immune Response in Randomized Clinical Trial
+AS03
Without adjuvant
+MF59
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Mt. Fuji from Murayama-campus, NIID, Tokyo
Mt. Fuji from Murayama-campus, NIID, Tokyo
Thank youThank you