7. vaccines

Question 1

define immunisation

Answer 1

an artificial process by which an individual is rendered immune

Question 2

define passive immunity

Answer 2

no immune response in recipient

Question 3

active immunisation

Answer 3

(vaccination)

recipient develops protective adaptive immune response

Question 4

historical background: variolation

Answer 4

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

Question 5

historical background: Jenner

Answer 5

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

Question 6

passive immunity

Answer 6

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

Question 7

what are passive vaccines?

Answer 7

preparations of antibodies taken from hyperimmune donors

Question 8

examples of passive vaccines

Answer 8

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

Question 9

VZV exposure during pregnancy

Answer 9

can cause foetal complications

pregnant women should contact GP if exposed

Question 10

active immunity

Answer 10

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

Question 11

what is herd immunity?

Answer 11

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

Question 12

general principles of immunisation

Answer 12

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

Question 13

what goes into a vaccine?

Answer 13

antigen
adjuvants
excipients

Question 14

what are adjuvants?

Answer 14

immune potentiators to increase the immunogenicity of the vaccine

Question 15

what are excipients?

Answer 15

various diluents and additives required for vaccine integrity

Question 16

which vaccines are most effective?

Answer 16

those for disease where natural exposure results in protective immunity

Question 17

classifications of active vaccines

Answer 17

live-attenuated
inactivated (killed)
subunit

Question 18

how are live-attenuated vaccines created?

Answer 18

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

Question 19

examples of live-attenuated vaccines

Answer 19

measles
mumps
rubella
polio
BCG
cholera 
zoster
VZV
live influenza

Question 20

pros of live-attenuated vaccines

Answer 20

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

Question 21

cons of live-attenuated vaccines

Answer 21

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

Question 22

varicella zoster vaccine

Answer 22

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

Question 23

vzv features

Answer 23

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

Question 24

zoster vaccination

Answer 24

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

Question 25

poliomyelitis

Answer 25

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

Question 26

polio vaccines

Answer 26

sabin and salk

Question 27

sabin oral polio vaccine

Answer 27

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

Question 28

salk infected polio vaccine

Answer 28

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

Question 29

what happens during tuberculosis infection?

Answer 29

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

Question 30

TB vaccination

Answer 30

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

Question 31

killed vaccines

Answer 31

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

Question 32

killed vaccines examples

Answer 32

hepatitis A | influenza

Question 33

pros of killed vaccines

Answer 33

no potential for reversion safe for immunocompromised stable in storage

Question 34

cons of killed vaccines

Answer 34

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

Question 35

influenza virus structure

Answer 35

``` 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 ```

Question 36

difficulties of influenza vaccination

Answer 36

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

Question 37

subunit vaccines

Answer 37

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

Question 38

toxoids

Answer 38

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

Question 39

tetanus immunity

Answer 39

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)

Question 40

polysaccharide capsules

Answer 40

eg Streptococcus pneumonia, Neisseria meningitidis | thick polysaccharide coats make them resistant to phagocytosis

Question 41

polysaccharide capsule vaccinations

Answer 41

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)

Question 42

vaccine conjugation

Answer 42

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

Question 43

recombinant protein subunit vaccine

Answer 43

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

Question 44

hpv vaccine

Answer 44

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)

Question 45

pros of subunit vaccines

Answer 45

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

Question 46

cons of subunit vaccines

Answer 46

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

Question 47

adjuvants

Answer 47

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

Question 48

novel approaches to vaccines

Answer 48

dna vaccines | viral vector

Question 49

DNA vaccines

Answer 49

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

Question 50

viral vector

Answer 50

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