9 - ebola Flashcards by Sylvie Wilson

biological warfare agents

microorganisms that give rise to disease

often inhaled causing systemic infection
low infectious dose

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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

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WHO opinion on vaccines and clean water

“most important public health interventions”

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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

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most commonly used conjugate vaccine

Hib vaccine

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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

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what is the Hib vaccine

Haemophilus influenzae type B vaccine

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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

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tularemia

disease caused by the bacterium Francisella tularensis
mainly affects mammals
causes prolonged fever, fatige and can be fatal

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antibiotics to treat tularemia

include streptomycin, gentamicin, doxycycline, and ciprofloxacin.

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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

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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

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attenuated vaccines

pathogen is altered so its virulence is reduced

pathogen is still alive

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properties of biological warfare agents

difficult to treat
often zoonotic diseases
infectious via inhalation route
cause endemic disease
low infectious dose

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2 pathogens tested in operation whitecoat

francisella tularensis

coxiella burnetti

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evidence that vaccines are effective

smallpox declared eradicated globally by WHO in 1980

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intracellular pathogen

enters body and infects hosts cells

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Burkholderia pseudomallei

intracellular pathogen causing meliodiosis
high mortality rates
common in tropical climates
latent in the host

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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