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CURRENT VACCINE APPROACHESCURRENT VACCINE APPROACHES
1
ISAWUMI ABIOLA
. . NOT ABIOLA!. . NOT ABIOLA!
2
EBOLA AND ITS MESS!!!
TRUE LOVE
BACKGROUND
• Viral Disease – EBV, EHF or VHF (Sub-Saharan
Africa)
• Five Strains:: 1976 (SUDV, EBOVEBOV). 1989
(RESTV). 1994 (BABD). 2008 (TAFV)
• Human Disease: EBOV, SUDV, TAFV, BABD.
Non-Human Primate Disease – RESTV.
• 25-90% death risk, average of 50%
• 1976-2013: 24 outbreaks, 1716 deaths.
December 2013-January 2016:: 28, 637 cases,
11, 315 deaths (Largest outbreak, West Africa).
• Genome - 7 genes (3'-NP-VP35-VP40-GP-VP30-
VP24-L-5').
3
TRANSMISSION AND SYMPTOMS
4
Microbes and Infection, 2005, The Natural History of Ebola Virus in Africa
TREATMENT
• Ebola Vaccines Investigation
• Trials of vaccine candidates
5
CURRENT VACCINES DEVELOPMENT
• Anti-GP antibodies (acute infection)
• Longer term protection (CD8/T cell/cytokine)
• Use non-replicating form of virus
• Adenovirus can deliver GP,
but many are immune to human vectors
APPROACH - Viral Vector Vaccine
• Chimpanzee adenovirus vector
• Vesicular stomatitis virus vector
6
Drug Discovery Development, Associated Press, 2014.
Chimpanzee Adenovirus
Vaccine
• Chimp-Adenovirus vaccine generates acute and
durable protective immunity against EBOV.
• Current one: Chim-Adenovirus type 3 (cAd3)
• cAd3-EBOZ, (MVA-BN).
• Mechanism:
• Genetically engineered to express Gp from EBV to provoke
an immune system against them.
• Immunological goal: Induction of effective antibody and
CD8 cell responses.
• Progress: Phase III
• Success: Acceptable safety profile, Effective and
immunogenic (I & II).
7
Drug Discovery Development, Associated Press, 2014.
Mechanism . .
Vesicular Stomatitis Virus Vector
• VSV-EBOV - Recombinant, replication-competent
vaccine.
• Genetically engineered to express Ebola glycoproteins to
provoke an immune response against the complete Ebola
virus.
Vaccine Variants: rVSV-ZEBOV, rVSV-ZEBOV-GP,
VSVΔG- ZEBOV, or BPSC1001.
Mechanism: Aims to induce EVD-specific immune responses
Progress: Phase III Success: Safety and effective( I & II )
8
ZMAPP
• ZMapp is an experimental biopharmaceutical drug
under development (immunotherapy).
• Three chimeric monoclonal antibodies (c13C6, c2G4,
and c4G7) which are neutralizing antibodies.
• Mechanism:
• The three antibodies block or neutralize the virus
by binding to or coating a different site on the
covering or envelope of the virus.
9
10
Vaccine Associated organisations Status (as of October 2015)
Chimp adenovirus 3 vectored
glycoprotein (cAd3-EBO Z)
GSK & NIAID Phase III in progress
rVSV vectored glycoprotein (VSV-
EBOV)
Newlink Genetics & Merck Interim Phase III results published
Human adenovirus 5 vectored
2014 glycoprotein insert
BIT & CanSino Phase I complete
Adenovirus 26 vectored
glycoprotein / MVA-BN
(Ad26.ZEBOV/ MVA-BN)
Johnson & Johnson Phase II in progress
MVA vectored glycoprotein Emergent Biosolutions Phase I planned
Glycoprotein nanoparticle +
MatrixM (Ebola GP vaccine)
Novavax Phase I complete
Oral human adenovirus 5 + TLR3
ligand
Vaxart Phase I planned
HPIV-3 vectored glycoprotein Russian Federal Ministry of Health Phase I planned
rVSVN4CT1 VesiculoVax Profectus Biosciences Phase I planned
Rabies vectored glycoprotein Jefferson University Non-human primate challenge complete
DNA vaccine Inovio Phase I planned
Purified glycoprotein Protein Sciences NHP challenge initiated
Ebola ∆VP30 H2O2 treated University of Wisconsin Non-human primate challenge complete
EBOLA VACCINE DEVELOPMENT ONGOING
• Convalescent plasma
Studies (immunotherapy)
• TKM-100802 Lipid
nanoparticle small
interfering Ribonucleic
acid (siRNA)
• Hyperimmune globulin
• AVI 7537 (Sarepta)
Phosphoro- diamidate
oligonucleotide
• Favipivavir/T-705
• BCX4430 (Biocryst
• Interferons
Antivirals
BEYOND EBOLA . .
• Ebola virus
• Chikungunya virus
• Marburg virus
• Rift valley fever virus
• MERS coronavirus
• Pandemic influenza
• SARS coronavirus
• Lassa virus
• Crimean-Congo
• hemorrhagic fever virus
• Enterovirus 71
• Hendra virus
• Monkeypox virus
• Nipah virus
• Venezuelan equine encephalitis
virus
• West Nile virus
No licensed human vaccine for any of these!
12
All correspondence to:
isawumiabiola@gmail.com
Unless otherwise stated, all pictures are Google sourced

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EBOLA NOT ABIOLA

  • 1. CURRENT VACCINE APPROACHESCURRENT VACCINE APPROACHES 1 ISAWUMI ABIOLA . . NOT ABIOLA!. . NOT ABIOLA!
  • 2. 2 EBOLA AND ITS MESS!!! TRUE LOVE
  • 3. BACKGROUND • Viral Disease – EBV, EHF or VHF (Sub-Saharan Africa) • Five Strains:: 1976 (SUDV, EBOVEBOV). 1989 (RESTV). 1994 (BABD). 2008 (TAFV) • Human Disease: EBOV, SUDV, TAFV, BABD. Non-Human Primate Disease – RESTV. • 25-90% death risk, average of 50% • 1976-2013: 24 outbreaks, 1716 deaths. December 2013-January 2016:: 28, 637 cases, 11, 315 deaths (Largest outbreak, West Africa). • Genome - 7 genes (3'-NP-VP35-VP40-GP-VP30- VP24-L-5'). 3
  • 4. TRANSMISSION AND SYMPTOMS 4 Microbes and Infection, 2005, The Natural History of Ebola Virus in Africa
  • 5. TREATMENT • Ebola Vaccines Investigation • Trials of vaccine candidates 5
  • 6. CURRENT VACCINES DEVELOPMENT • Anti-GP antibodies (acute infection) • Longer term protection (CD8/T cell/cytokine) • Use non-replicating form of virus • Adenovirus can deliver GP, but many are immune to human vectors APPROACH - Viral Vector Vaccine • Chimpanzee adenovirus vector • Vesicular stomatitis virus vector 6 Drug Discovery Development, Associated Press, 2014.
  • 7. Chimpanzee Adenovirus Vaccine • Chimp-Adenovirus vaccine generates acute and durable protective immunity against EBOV. • Current one: Chim-Adenovirus type 3 (cAd3) • cAd3-EBOZ, (MVA-BN). • Mechanism: • Genetically engineered to express Gp from EBV to provoke an immune system against them. • Immunological goal: Induction of effective antibody and CD8 cell responses. • Progress: Phase III • Success: Acceptable safety profile, Effective and immunogenic (I & II). 7 Drug Discovery Development, Associated Press, 2014. Mechanism . .
  • 8. Vesicular Stomatitis Virus Vector • VSV-EBOV - Recombinant, replication-competent vaccine. • Genetically engineered to express Ebola glycoproteins to provoke an immune response against the complete Ebola virus. Vaccine Variants: rVSV-ZEBOV, rVSV-ZEBOV-GP, VSVΔG- ZEBOV, or BPSC1001. Mechanism: Aims to induce EVD-specific immune responses Progress: Phase III Success: Safety and effective( I & II ) 8
  • 9. ZMAPP • ZMapp is an experimental biopharmaceutical drug under development (immunotherapy). • Three chimeric monoclonal antibodies (c13C6, c2G4, and c4G7) which are neutralizing antibodies. • Mechanism: • The three antibodies block or neutralize the virus by binding to or coating a different site on the covering or envelope of the virus. 9
  • 10. 10 Vaccine Associated organisations Status (as of October 2015) Chimp adenovirus 3 vectored glycoprotein (cAd3-EBO Z) GSK & NIAID Phase III in progress rVSV vectored glycoprotein (VSV- EBOV) Newlink Genetics & Merck Interim Phase III results published Human adenovirus 5 vectored 2014 glycoprotein insert BIT & CanSino Phase I complete Adenovirus 26 vectored glycoprotein / MVA-BN (Ad26.ZEBOV/ MVA-BN) Johnson & Johnson Phase II in progress MVA vectored glycoprotein Emergent Biosolutions Phase I planned Glycoprotein nanoparticle + MatrixM (Ebola GP vaccine) Novavax Phase I complete Oral human adenovirus 5 + TLR3 ligand Vaxart Phase I planned HPIV-3 vectored glycoprotein Russian Federal Ministry of Health Phase I planned rVSVN4CT1 VesiculoVax Profectus Biosciences Phase I planned Rabies vectored glycoprotein Jefferson University Non-human primate challenge complete DNA vaccine Inovio Phase I planned Purified glycoprotein Protein Sciences NHP challenge initiated Ebola ∆VP30 H2O2 treated University of Wisconsin Non-human primate challenge complete EBOLA VACCINE DEVELOPMENT ONGOING • Convalescent plasma Studies (immunotherapy) • TKM-100802 Lipid nanoparticle small interfering Ribonucleic acid (siRNA) • Hyperimmune globulin • AVI 7537 (Sarepta) Phosphoro- diamidate oligonucleotide • Favipivavir/T-705 • BCX4430 (Biocryst • Interferons Antivirals
  • 11. BEYOND EBOLA . . • Ebola virus • Chikungunya virus • Marburg virus • Rift valley fever virus • MERS coronavirus • Pandemic influenza • SARS coronavirus • Lassa virus • Crimean-Congo • hemorrhagic fever virus • Enterovirus 71 • Hendra virus • Monkeypox virus • Nipah virus • Venezuelan equine encephalitis virus • West Nile virus No licensed human vaccine for any of these!
  • 12. 12 All correspondence to: isawumiabiola@gmail.com Unless otherwise stated, all pictures are Google sourced