Download Vaccines for Ebola

PHM142 Fall 2016
Coordinator: Dr. Jeffrey Henderson
Instructor: Dr. David Hampson
Ebola Vaccines
Daniela Fernandes, Becky Wright, Leah Egan, Briana
Genge
Ebola Virus
Ebola virus (EBOV) belongs to the filoviridae family -- it’s a single stranded negative sense RNA
5 known strains of the virus:
● Zaire ebolavirus
● Sudan ebolavirus
● Reston ebolavirus (not pathogenic in humans)
● Côte d’Ivoire ebolavirus
● Bundibugyo ebolavirus
Source: studymedia.in
Contracted via direct contact with bodily fluids of an infected person, contaminated objects, fruit
bats and other primates, and semen of a recovered man
Infects dendritic cells, macrophages and monocytes via a mechanism mediated by its surface
glycoprotein
Results in hemorrhagic fever and causes death in 90% of cases
Source: Biomedical Waste Solutions
Ebola Pathophysiology
● Ebola virus triggers an
overexpression of
cytokines resulting in
reduced vascular stability
● Glycoprotein interferes with
signaling of white blood
cells and inhibits
activation of immune
system
● Ebola virus has a wide cell
tropism. It has the ability to
infect a variety of different
cell types, but mainly
infects cells in the lymphoid
tissue, liver and spleen
Source: Journal of Virology
Ebola Diagnosis
● Early diagnosis of Ebola is difficult because symptoms are nonspecific to Ebola infection
● Ebola Virus is only detectable in the blood a few days after symptoms begin
● Lab tests used in diagnosis include:
Timeline of Infection
Within a few days after symptoms begin
Diagnostic Tests Available
●
●
●
●
Polymerase chain reaction (PCR)
Antigen-Capture enzyme-linked
immunosorbent assay (ELISA) testing
IgM ELISA
Virus isolation
Later in disease course or after recovery
●
IgM and IgG antibodies
Retrospectively in deceased patients
●
●
●
Immunohistochemistry testing
PCR
Virus isolation
Source: Centers for Disease Control and Prevention
Challenge
Solutions
● Viral Vectors
EBOV GP non-infectious on its own
● Saponin Adjuvant
EBOV viral Structure
Glycoprotein coat (covered in Nlinked glycans)
Ebola virus genetic material
Ebola virus cell invasion
Macrophage
Phagocytosed Ebola virus
Mechanism of VSV-EBOV vaccine
Vesicular stomatitis virus native
glycoprotein coat
Live attenuated vesicular
stomatitis virus
Ebola virus glycoprotein coat
Mechanism of VSV-EBOV vaccine
Glycoprotein specific antibody
Macrophage
Phagocytosed Ebola virus
Matrix-M (Novavax)
• Saponin-based adjuvant (with cholesterol and phospholipid)
• Enhances cellular response to viral protein
• Dose-sparing
• Activates many immune cell types
• Mechanism of action unclear
Matrix-M results in enhanced Immune Response
Immune
Response
&
Memory
Matrix-M
MHC II
Expression
Activated
immune
cells
Antigen
Presentation
CD 4+ T
Cells
Multifunctional T
Cells
IFN-𝛄
IgG Class
Switching
Benefits of Matrix-M
• Reduced costs
• Reduced toxicity
• Dose-Sparing
SUMMARY
● Ebola virus is a single stranded negative sense RNA belonging to the filoviridae family
● The virus infects dendritic cells, monocytes and macrophages
● Infection results in:
❖ An overexpression of cytokines causing reduced vascular
stability and eventually hemorrhage
❖ No immune system activation due to EBOV glycoprotein
interfering with WBC signalling
● Common diagnostic tests include ELISA and PCR
● VSV EBOV vaccine uses a live attenuated vaccine
❖ It replaces the native glycoprotein coat with that of the
ebola virus in order to raise immunity in the patient
● Matrix-M is a saponin-based adjuvant that enhances the cellular immune response to
viral glycoproteins during nanoparticle vaccination
❖ It activates many immune cells including CD4+ T cells
❖ It results in longer lasting and increased levels of antibodies via
multifunctional T cell activation
❖ Utilizes IFN-gamma to achieve its enhanced immune response
References
Feldmaan, H. (2011) Ebola haemorrhagic fever. Lancet. 377, 849–862
Callaway, E. (2015) Successful Ebola vaccine provides 100% protection in trial. Nat. News. 3 July 2016
Lee, J. E., Road, T. P., and Jolla, L. (2009) Ebolavirus glycoprotein structure and mechanism of entry. Futur. Virol. 4, 621–635
Kaner, J, Schaack, S. (2016) Understanding Ebola: the 2014 epidemic. Global Health. 12, 53
Mohan G et al. (2015) Less Is More: Ebola Virus Surface Glycoprotein Expression Levels Regulate Virus Production and Infectivity. J Virol. 15, 1205-17
World Health Organization. (2016) Ebola virus disease. [online]
Sullivan, N. Yang, Z-Y., Nabel, G. J. (2013) Ebola Virus Pathogenesis: IMplications For Vaccines And Therapies. J Virol. 77.18, 9733-9737
BMJ. (2016) Ebola virus infection. [online]
Center for Disease Control and Prevention. (2015) Ebola virus disease. [online]
Bengtsson LK, Song H, et al. (2016) Matrix-M adjuvant enhances antibody, cellular and protective immune responses of a Zaire Ebola/Makona virus
glycoprotein (GP) nanoparticle vaccine in mice. Vaccine. 34, 1927-1935
Novaxax, Matrix-M Adjuvant Technology. [online]
Novavax. (2014) Press Release: Novavax Announces Ebola Vacine Development Program at the 8th Vaccine and ISV Conference in Philadelphia.
[online]
Schroder K, Hertzog PJ, Ravasi T, Hume DA. (2004) Interferon-gamma: an overview of signals, mechanisms and functions. Journal of Leukocyte
Biology. 75, 163-189