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Ebolavirus
Ecology and antiviral strategies
Ayato Takada
Hokkaido University
Research Center for Zoonosis Control
IRIDeS Plenary Session in One Health Summit 2015
Davos. October 5, 2015
Filovirus
Ebolavirus
Marburgvirus
Cuevavirus
Bundibugyo ebolavirus (2008)
Tai Forest ebolavirus (1994)
Zaire ebolavirus (1995)
Zaire ebolavirus (1976)
Reston ebolavirus (1989)
Reston ebolavirus (1992)
Sudan ebolavirus (1976)
Sudan ebolavirus (1979)
Lloviu virus (2011)
Marburg marburgvirus (2005)
Marburg marburgvirus (1980)
100
Species Genus
Marburgvirus
Ebolavirus
Cuevavirus
Angola
Kenya
RC
Gabon
Uganda
South Africa
Zimbabwe
Zaire ebolavirus
Marburgvirus
Sudan ebolavirus
Taï Forest ebolavirus
Bundibugyo ebolavirus
South
Sudan
2001-02, 02-03, 03, 05
2004-05
DRC
1976, 79, 2004
1975
1996
1975
1994, 96, 96-97, 2001-02
2000-01, 11, 12
2007
2007, 12
1980, 87
1976, 77, 95, 2007, 08-09
2012
1998-2000
Guinea
Cote
d’Ivoire
Liberia
Sierra Leone Nigeria
2014 2014
1994
2014
2014Senegal
2014
2014
Mali
Filovirus diseases in Africa (~2014)
Natural host
Vaccine and therapy
Diagnosis
Natural host
Vaccine and therapy
Diagnosis
Bundibugyo ebolavirus (2008)
Tai Forest ebolavirus (1994)
Zaire ebolavirus (1995)
Zaire ebolavirus (1976)
Reston ebolavirus (1989)
Reston ebolavirus (1992)
Sudan ebolavirus (1976)
Sudan ebolavirus (1979)
Lloviu virus (2002)
Marburg marburgvirus (2005)
Marburg marburgvirus (1980)
100
human, monkey
human
human, monkey(fruit bat, duiker, dog)
human
monkey, pig (human, fruit bat)
human, monkey, fruit bat
Filovirus species
insectivorous bat
Animals
Filoviruses and infected animals
PLoS Pathogens
Vol. 5, 2009
Virus-specific antibodies (IgG), but not viral
genome, are continuously detected in bats
PC
PC
Ndola
Suesueman (FB)Ndola Kasanka
Bundibugyo ebolavirus (2008)
Tai Forest ebolavirus (1994)
Zaire ebolavirus (1995)
Zaire ebolavirus (1976)
Reston ebolavirus (1989)
Reston ebolavirus (1992)
Sudan ebolavirus (1976)
Sudan ebolavirus (1979)
Lloviu virus (2011)
Marburg marburgvirus (2005)
Marburg marburgvirus (1980)
100
種 属
Marburgvirus
Ebolavirus
Cuevavirus
Species Genus
Distribution of filoviruses?
Natural host
Vaccine and therapy
Diagnosis
Natural host
Vaccine and therapy
Diagnosis
Vesicular stomatitis virus (VSV)-based
recombinant vaccine
VSV
GNP VP35 VP40 LGP VP30 VP24
Ebolavirus
GP
Vesicular stomatitis virus (VSV)-based
recombinant vaccine
NP VP35 VP40 LGP VP30 VP24
Ebolavirus
GP
VSV-EBOV
N P M LGP
Natural host
Vaccine and therapy
Diagnosis
Natural host
Vaccine and therapy
Diagnosis
Genetic engineering of monoclonal antibodies for
antibody therapy
Mouse Chimeric HumanHumanized
Fc
Fab
Derived from
mouse
Derived from
mouse
Bundibugyo ebolavirus (2008)
Tai Forest ebolavirus (1994)
Zaire ebolavirus (1995)
Zaire ebolavirus (1976)
Reston ebolavirus (1989)
Reston ebolavirus (1992)
Sudan ebolavirus (1976)
Sudan ebolavirus (1979)
Lloviu virus (2011)
Marburg marburgvirus (2005)
Marburg marburgvirus (1980)
100
種 属
Marburgvirus
Ebolavirus
Cuevavirus
・ Due to the large antigenic difference among ebolavirus species,
previously tested antibodies are only effective against Zaire ebolavirus
・Outbreaks with other ebolaviruses (i.e., Sudan and Bundibugyo)
repeatedly occur in Central Africa.
Phylogenetic relationship among filoviruses
Nucleotide analogs
Brincidofovir
Lamivudine
Favipiravir
Natural host
Vaccine and therapy
Diagnosis
Natural host
Vaccine and therapy
Diagnosis
Diagnosis of EVD
・Virus isolation
・Viral RNA detection(PCR, LAMP)
・Antibody detection(ELISA)
・Antigen detection(Immunochromatography)
PC
PC
Ndola
Suesueman (FB)Ndola Kasanka
• Lack of appropriate field adapted tests
• Other diseases with similar symptoms
• Characteristics of regions that have
recorded large outbreaks:
oRemote areas
oLimited medical, public health, transportation
and communication infrastructure
oDelayed confirmatory diagnosis
oIncreased secondary transmission
• Early diagnosis requires antigen detection
test that is simple, stable and rapid
Challenges to filovirus diagnosis
Immunochromatography kit for EVD diagnosis
Rapid diagnosis kit for EVD diagnosis
What we have to do against Ebola
• To find natural reservoirs and/or potential
carrier hosts.
• Development of antiviral treatments.
• Establishment of the early diagnosis system.
• Education: Dissemination of knowledge.
Hokkaido University Research Center
for Zoonosis Control
Hirohito Ogawa
Yuka Suzuki
Emiko Nakagawa
Akihiro Ishii
Reiko Yoshida
Masahiro Kajihara
Mieko Muramatsu
Makoto Kuroda
Junki Maruyama
Naganori Nao
Rashid Manzoor
Hiroko Miyamoto
Ayaka Yokoyama
Yasuhiko Suzuki
Kimihito Ito
Manabu Igarashi
Hirofumi Sawa
Chihiro Sugimoto
Ichiro Nakamura
Keita Matsuno
Funding:
・The Japan Initiative for Global Research Network on Infectious Diseases (J-GRID), Global COE
Program from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan
・Science and Technology Research Partnership for Sustainable Development (SATREPS) from JST/JICA,
Japan
National Institute of Infectious Diseases
Eri Nakayama
Masayuki Saijo
Shigeru Morikawa
University of Zambia
Aaron Mweene
Edgar Simulundu
Katendi Changula
Institut National de Recherche
Biomédicale
Jean-Jacques Muyembe
Stomy Karhemere bi Shamamba
Jastin Masumu
Jimmy Kapetshi
National Institute of Allergy and
Infectious Diseases
Heinz Feldmann
Andrea Marzi
Hideki Ebihara
Acknowledgments

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Ebolavirus: Ecology and Antiviral Strategies Ayato TAKADA

  • 1. Ebolavirus Ecology and antiviral strategies Ayato Takada Hokkaido University Research Center for Zoonosis Control IRIDeS Plenary Session in One Health Summit 2015 Davos. October 5, 2015
  • 2. Filovirus Ebolavirus Marburgvirus Cuevavirus Bundibugyo ebolavirus (2008) Tai Forest ebolavirus (1994) Zaire ebolavirus (1995) Zaire ebolavirus (1976) Reston ebolavirus (1989) Reston ebolavirus (1992) Sudan ebolavirus (1976) Sudan ebolavirus (1979) Lloviu virus (2011) Marburg marburgvirus (2005) Marburg marburgvirus (1980) 100 Species Genus Marburgvirus Ebolavirus Cuevavirus
  • 3. Angola Kenya RC Gabon Uganda South Africa Zimbabwe Zaire ebolavirus Marburgvirus Sudan ebolavirus Taï Forest ebolavirus Bundibugyo ebolavirus South Sudan 2001-02, 02-03, 03, 05 2004-05 DRC 1976, 79, 2004 1975 1996 1975 1994, 96, 96-97, 2001-02 2000-01, 11, 12 2007 2007, 12 1980, 87 1976, 77, 95, 2007, 08-09 2012 1998-2000 Guinea Cote d’Ivoire Liberia Sierra Leone Nigeria 2014 2014 1994 2014 2014Senegal 2014 2014 Mali Filovirus diseases in Africa (~2014)
  • 4. Natural host Vaccine and therapy Diagnosis
  • 5. Natural host Vaccine and therapy Diagnosis
  • 6. Bundibugyo ebolavirus (2008) Tai Forest ebolavirus (1994) Zaire ebolavirus (1995) Zaire ebolavirus (1976) Reston ebolavirus (1989) Reston ebolavirus (1992) Sudan ebolavirus (1976) Sudan ebolavirus (1979) Lloviu virus (2002) Marburg marburgvirus (2005) Marburg marburgvirus (1980) 100 human, monkey human human, monkey(fruit bat, duiker, dog) human monkey, pig (human, fruit bat) human, monkey, fruit bat Filovirus species insectivorous bat Animals Filoviruses and infected animals
  • 8.
  • 9. Virus-specific antibodies (IgG), but not viral genome, are continuously detected in bats PC PC Ndola Suesueman (FB)Ndola Kasanka
  • 10. Bundibugyo ebolavirus (2008) Tai Forest ebolavirus (1994) Zaire ebolavirus (1995) Zaire ebolavirus (1976) Reston ebolavirus (1989) Reston ebolavirus (1992) Sudan ebolavirus (1976) Sudan ebolavirus (1979) Lloviu virus (2011) Marburg marburgvirus (2005) Marburg marburgvirus (1980) 100 種 属 Marburgvirus Ebolavirus Cuevavirus Species Genus
  • 12. Natural host Vaccine and therapy Diagnosis
  • 13. Natural host Vaccine and therapy Diagnosis
  • 14. Vesicular stomatitis virus (VSV)-based recombinant vaccine VSV GNP VP35 VP40 LGP VP30 VP24 Ebolavirus GP
  • 15. Vesicular stomatitis virus (VSV)-based recombinant vaccine NP VP35 VP40 LGP VP30 VP24 Ebolavirus GP VSV-EBOV N P M LGP
  • 16.
  • 17. Natural host Vaccine and therapy Diagnosis
  • 18. Natural host Vaccine and therapy Diagnosis
  • 19. Genetic engineering of monoclonal antibodies for antibody therapy Mouse Chimeric HumanHumanized Fc Fab Derived from mouse Derived from mouse
  • 20.
  • 21.
  • 22.
  • 23. Bundibugyo ebolavirus (2008) Tai Forest ebolavirus (1994) Zaire ebolavirus (1995) Zaire ebolavirus (1976) Reston ebolavirus (1989) Reston ebolavirus (1992) Sudan ebolavirus (1976) Sudan ebolavirus (1979) Lloviu virus (2011) Marburg marburgvirus (2005) Marburg marburgvirus (1980) 100 種 属 Marburgvirus Ebolavirus Cuevavirus ・ Due to the large antigenic difference among ebolavirus species, previously tested antibodies are only effective against Zaire ebolavirus ・Outbreaks with other ebolaviruses (i.e., Sudan and Bundibugyo) repeatedly occur in Central Africa. Phylogenetic relationship among filoviruses
  • 25.
  • 26.
  • 27. Natural host Vaccine and therapy Diagnosis
  • 28. Natural host Vaccine and therapy Diagnosis
  • 29. Diagnosis of EVD ・Virus isolation ・Viral RNA detection(PCR, LAMP) ・Antibody detection(ELISA) ・Antigen detection(Immunochromatography) PC PC Ndola Suesueman (FB)Ndola Kasanka
  • 30. • Lack of appropriate field adapted tests • Other diseases with similar symptoms • Characteristics of regions that have recorded large outbreaks: oRemote areas oLimited medical, public health, transportation and communication infrastructure oDelayed confirmatory diagnosis oIncreased secondary transmission • Early diagnosis requires antigen detection test that is simple, stable and rapid Challenges to filovirus diagnosis
  • 32. Rapid diagnosis kit for EVD diagnosis
  • 33. What we have to do against Ebola • To find natural reservoirs and/or potential carrier hosts. • Development of antiviral treatments. • Establishment of the early diagnosis system. • Education: Dissemination of knowledge.
  • 34. Hokkaido University Research Center for Zoonosis Control Hirohito Ogawa Yuka Suzuki Emiko Nakagawa Akihiro Ishii Reiko Yoshida Masahiro Kajihara Mieko Muramatsu Makoto Kuroda Junki Maruyama Naganori Nao Rashid Manzoor Hiroko Miyamoto Ayaka Yokoyama Yasuhiko Suzuki Kimihito Ito Manabu Igarashi Hirofumi Sawa Chihiro Sugimoto Ichiro Nakamura Keita Matsuno Funding: ・The Japan Initiative for Global Research Network on Infectious Diseases (J-GRID), Global COE Program from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan ・Science and Technology Research Partnership for Sustainable Development (SATREPS) from JST/JICA, Japan National Institute of Infectious Diseases Eri Nakayama Masayuki Saijo Shigeru Morikawa University of Zambia Aaron Mweene Edgar Simulundu Katendi Changula Institut National de Recherche Biomédicale Jean-Jacques Muyembe Stomy Karhemere bi Shamamba Jastin Masumu Jimmy Kapetshi National Institute of Allergy and Infectious Diseases Heinz Feldmann Andrea Marzi Hideki Ebihara Acknowledgments