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204 theme 1 > 7. vaccines > Flashcards

7. vaccines Flashcards

1
Q

define immunisation

A

an artificial process by which an individual is rendered immune

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2
Q

define passive immunity

A

no immune response in recipient

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3
Q

active immunisation

A

(vaccination)

recipient develops protective adaptive immune response

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4
Q

historical background: variolation

A

variola (smallpox virus)
fluid harvested from pustules of recovering individuals
documented from 1000AD globally

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5
Q

historical background: Jenner

A

1796: fluid from cowpox lesions to protect against smallpox
first documented use of live-attenuated vaccine
= birth of modern immunisation

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6
Q

passive immunity

A

immunity conferred without active host response on behalf of recipient
protection is temporary

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7
Q

what are passive vaccines?

A

preparations of antibodies taken from hyperimmune donors

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8
Q

examples of passive vaccines

A

immunoglobulin replacement in antibody deficiency
VZV prophylaxis, eg during exposure during pregnancy
anti-toxin therapies, eg snake anti-serum

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9
Q

VZV exposure during pregnancy

A

can cause foetal complications

pregnant women should contact GP if exposed

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10
Q

active immunity

A

immunity conferred in recipient following generation of adaptive immune response
general principle = stimulate adaptive immune response without causing clinically apparent infection

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11
Q

what is herd immunity?

A

vaccination of sufficient numbers impact transmission dynamic, so even unimmunised individuals are low risk

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12
Q

general principles of immunisation

A

given to healthy individuals prior to pathogen exposure
generate long lasting, high affinity IgG antibody response
strong CD4 T cell response is prerequisite

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13
Q

what goes into a vaccine?

A

antigen
adjuvants
excipients

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14
Q

what are adjuvants?

A

immune potentiators to increase the immunogenicity of the vaccine

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15
Q

what are excipients?

A

various diluents and additives required for vaccine integrity

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16
Q

which vaccines are most effective?

A

those for disease where natural exposure results in protective immunity

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17
Q

classifications of active vaccines

A

live-attenuated
inactivated (killed)
subunit

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18
Q

how are live-attenuated vaccines created?

A

prolonged culture ex vivo in non physiological conditions
selected variants adapted to live in culture
variants are viable in vivo, but no longer able to cause disease

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19
Q

examples of live-attenuated vaccines

A 
measles
mumps
rubella
polio
BCG
cholera 
zoster
VZV
live influenza
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20
Q

pros of live-attenuated vaccines

A

replication within hot, produces highly effective and durable response
in viral vaccine, intracellular infection leads to good CD8 response
repeated boosting not required
in some disease, may get secondary protection of unvaccinated individuals

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21
Q

cons of live-attenuated vaccines

A

storage problems, short half life
may revert to wild type
immunocompromised recipients may develop clinical disease

22
Q

varicella zoster vaccine

A

primary infection = chickenpox
cellular and humeral immunity provide lifelong protection
viral reaction = zoster
particularly elderly, fairly debilitating, may cause long term neuropathic pain

23
Q

vzv features

A

live attenuated
95% effective at preventing chickenpox
attenuated virus does establish infection of sensory ganglia
not on UK schedule

24
Q

zoster vaccination

A

similar to vzv preparation, much higher dose
aims to boost memory t cell responses to vzv
reduces severity and zoster incidence in elderly

25
Q

poliomyelitis

A

enterovirus establishes infection in oropharynx and GI tract (alimentary phase)
spreads to peyers patches, disseminated via lymphatics
haematogenous spread (viraemia phase)
1% patients develop neurological phase: replication in motor neurone in spinal cord, brainstem and motor cortex

26
Q

polio vaccines

A

sabin and salk

27
Q

sabin oral polio vaccine

A

live attenuated
viable virus recovered from stool after immunisation
highly effective - some protection in non-immunised population
1/7500000 vaccine associated paralytic polio

28
Q

salk infected polio vaccine

A

inactivated
effective, but herd immunity inferior
used where risk of contraction is less
less risk

29
Q

what happens during tuberculosis infection?

A

during primary infection, MTB establishes infection within phase-lysosomes of macrophages
macrophages present TB antigen to MTB specific CD4 t cells
secrete IFN-g
activated macrophages encase TB in granuloma

30
Q

TB vaccination

A

only licensed product is BCG
produced by repeat passage of non-tuberculous mycobacterium
aims to increase Th1 cell responses to M bovis - conferring protection against MTB
given by intradermal infection
80% effective in preventing disseminated tb/tb meningitis in children
little effect on pulmonary tb

31
Q

killed vaccines

A

entire organism used, but physical/chemical methods destroy viability
stimulates b cells, taken up by antigen-presenting cells to stimulate antigen specific cd4 cells
minimal cd8 response?
responses are less robust than live attenuated

32
Q

killed vaccines examples

A

hepatitis A

influenza

33
Q

pros of killed vaccines

A

no potential for reversion
safe for immunocompromised
stable in storage

34
Q

cons of killed vaccines

A

mainly cd4/antibody response
responses less durable than live responses - boosters required
higher uptake generally required for herd immunity

35
Q

influenza virus structure

A 
internal antigens = type specific proteins (matrix, RNP), used to determine particular virus, ie  A, B or C
external antigens (haemagglutinin and neuraminidase) , subtype and strain specific antigens of influenza A
36
Q

difficulties of influenza vaccination

A

target antigens are prone to mutation (antigenic drift) - seasonal variation
CDC provide candidate virus strains to manufacture, infected into fertilised hen eggs then virus is harvested
major changes can occur when viral strains recombine

37
Q

subunit vaccines

A

uses only critical part of the organism
components may be: purified from organism, generated by recombinant techniques
protection depends on eliciting CD4 and antibody responses

38
Q

toxoids

A

relate to toxin-producing bacteria
eg Clostridium tetani, Bordatella pertussis
toxins are chemically detoxified to form toxoids
retain immunogenicity
stimulate antibody response, antibodies neutralise toxin

39
Q

tetanus immunity

A

performed by high affinity IgG antibodies - neutralise toxin molecules in circulation
immune complexes are removed in spleen
anti-toxin can be given in established cases (passive immunisation)

40
Q

polysaccharide capsules

A

eg Streptococcus pneumonia, Neisseria meningitidis

thick polysaccharide coats make them resistant to phagocytosis

41
Q

polysaccharide capsule vaccinations

A

made from purified polysaccharide coats
aim to induce IgG antibodies to improve opsonisation
suboptimal - polysaccharides are weakly immunogenic
stimulate small population of t-independent t cells (no t cell response)

42
Q

vaccine conjugation

A

naïve b cell expressing surface IgM recognises polysaccharide antigen - internalised with protein conjugate
conjugate processed in class II pathway
naïve b cells present peptides from conjugate to Th cell
t cell helps b cell perform affinity maturation
antibody = specific for polysaccharide not protein conjugate

43
Q

recombinant protein subunit vaccine

A

proteins expressed in lower organisms
purified to produce vaccine
hep B surface antigen, hpv vaccine

44
Q

hpv vaccine

A

hpv subtypes 16 and 18 = major causal factor in cervical carcinoma
vaccine development = problematic as hpv difficult to culture
subunit vaccines are ‘empty virus particles’, prevent primary infection
quadravalent vaccine cover additional hpv strains (genital warts, penile cancer)

45
Q

pros of subunit vaccines

A

extremely safe
work well where primary infection may be prevented by an antibody response
works when virus cannot be cultured, eg hpv, hep B

46
Q

cons of subunit vaccines

A

development required detailed knowledge of virology, pathogenesis and immunology
specialised and expensive production
weaker immune responses - boosting often required

47
Q

adjuvants

A

widely used, mechanism poorly understood
eg. alum lipopolysaccharide bind to prrs on apcs - enhances costimulation and cytokine secretion
important field for development
novel adjuvants = tlr ligands, eg CPG repeats

48
Q

novel approaches to vaccines

A

dna vaccines

viral vector

49
Q

DNA vaccines

A

plasma DNA encodes vaccine antigen of interest applied
taken up by cells, transcribed and translated
elicits host immune response
mainly performed in mice models
poorly immunogenic in human trials

50
Q

viral vector

A

benign virus can be easily grown in culture engineered to carry genes encoding immunogenic antigens
watered virus used as live attenuated vaccine
use restricted to animals to date

204 theme 1 (12 decks)

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