9 - ebola Flashcards
biological warfare agents
microorganisms that give rise to disease
often inhaled causing systemic infection
low infectious dose
operation whitecoat 1954
biodefense medical research program
injected consciencous objectors with vaccines against known used pathogens
purpose to defend troops against attacks using biological warfare agents
WHO opinion on vaccines and clean water
“most important public health interventions”
stages of vaccine development
- research –> target discovery, identify antigens, manufacture vaccine
- pre-clinical –> test potency, safety, animal testing
- clinical –> test vaccine on humans in clinical trials
most commonly used conjugate vaccine
Hib vaccine
aim and mechanism behind conjugate vaccines
covalently bond a weak polysaccharide antigen to a strong carrier protein antigen to induce a stronger immunological response to the weak antigen
T helper cells produced as well as antibodies
IgG –> IgM
more specific B type memory cells
what is the Hib vaccine
Haemophilus influenzae type B vaccine
evidence that Hib vaccine is effective
In countries that include it as a routine vaccine, rates of severe Hib infections have decreased more than 90%
resulted in a decrease in the rate of meningitis, pneumonia, and epiglottitis
tularemia
disease caused by the bacterium Francisella tularensis
mainly affects mammals
causes prolonged fever, fatige and can be fatal
antibiotics to treat tularemia
include streptomycin, gentamicin, doxycycline, and ciprofloxacin.
tularemia vaccine
live attenuated vaccine
–> has been used in humans but risk of transferral of microorganism to other people
vaccine is currently under review by the FDA
why is tularemia good as a bioterrorism agent
the bacteria can be freeze-dried into a power which can be aerosolized
only a few inhaled bacteria necessary to cause disease
attenuated vaccines
pathogen is altered so its virulence is reduced
pathogen is still alive
properties of biological warfare agents
difficult to treat often zoonotic diseases infectious via inhalation route cause endemic disease low infectious dose
2 pathogens tested in operation whitecoat
francisella tularensis
coxiella burnetti
evidence that vaccines are effective
smallpox declared eradicated globally by WHO in 1980
intracellular pathogen
enters body and infects hosts cells
Burkholderia pseudomallei
intracellular pathogen causing meliodiosis
high mortality rates
common in tropical climates
latent in the host
vaccine development for Burkholderia pseudomallei
no vaccine has produced complete protection in animal models
more required than just antibodies due to intracellular lifestyle
manno-heptopyranose capsule
extracellular capsular polysaccharide (CPS) produced by Burkholderia pseudomallei
1E10
mutant Burkholderia pseudomallei
couldnt make necessary CPS
didnt cause disease in animals
couldnt function as a vaccine when animal infected with Burkholderia pseudomallei
importance of capsule in protection against Burkholderia pseudomallei
immune response against pathogen with CPS provides immunity against Burkholderia pseudomallei
research focussing on conjugate vaccine to use as a vaccine
live vaccines disadvantages
hazardous
biological conjugation
takes advantage of the natural bacteria glycosylation system to produce vaccines
bacterial glycosylation
bacteria naturally glycosylate proteins (add sugar molecules to them)
method of biological conjugation
join sugar molecule (o-antigen) and protein using glycosyltransferase enzyme
extract molecule and purify and use that for vaccine
results of biological conjugation for F. tularensis
mice injected with conjugate vaccine and infected with tularensis
half animals survive when using adjuvant
effect of respiratory challenge dose for tularensis
even if you have the vaccine, at a high challenge dose almost everyone gets sick
adjuvant
added to a vaccine to enhance the body’s immune response to an antigen
–> increased antibody production
future bacterial vaccine work
look at different types of adjuvant
investigate different routes of administration/inoculation
use different animal models (mice not good) –> use primates
test approaches against other pathogens
ebola
haemorragic virus
animal reservoir for ebola
bats and primates
effects of ebola once infected humans
high fever/flu-like mostly and muscle pain
rapid progression of disease
some get vomiting, uncontrolled haemorrhage, skin rash, seizure
mechanism of ebola infection
infects via inhalation
crosses epithelium and enters immune cells (DCs)
immune evasion:
suppresses IFN-y and inhibits DC maturation
also causes cytokine storm –> causes fever
virus disseminates systemically and replicates within cells
breakdown of organs –> vascular leakage –> haemorrhage
when was the ebola outbreak
2014-2016 west africa
10,000 deaths
mortality rate of ebola in 2014 outbreak
40%
why did the ebola outbreak spread
cultural interaction with the dead and ill
sierra leone
remaining challenges after 2014 ebola outbreak
- residual risk surveillance
- survival engagement and care (transmission of ebola by ebola survivors e.g. by semen)
- rebuilding health infrastructure
UK contribution to ebola by DSTL
looked at developing therapeutics/vaccines
diagnosis:
- take blood from patients
- inactivate ebola virus (using AVL buffer and incubation at 60 degrees for 15 minutes)
- pass blood through diagnostic test
ebola diagnostic tests
film array
lateral flow device (antibody test)
film array
material put in pouch
a number of PCR reactions carried out very quickly
compares virus against known pathogens
identified many people as sick from other diseases with similar symptoms to ebola –> stopped spreading of ebola
film arrary disadvantages
needs power
needs complex reagents
needs clean laboratory
lateral flow device
inactivated antibody conjugated to molecule that changes colour in presence of ebola
viral vaccines
most based on viral glycoproteins
political effect on vaccine development
in circumstance of outbreak can increase speed of vaccine development due to lifting rules or providing funding
get WHO involved
