The emergence of viral diseases with serious public health effects demands prompt research intervention and attention, especially in the developing countries. Such is EBOLA among other neglected but potentially dangerous diseases. This presentation seeks to underline the current vaccine challenges and provides possible pointers to match its effects.
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
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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).
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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 )
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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.
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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!