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311 - Molecular Immunology > 16 - Types of Vaccines - Watson > Flashcards

16 - Types of Vaccines - Watson Flashcards

1
Q

Name all the different vaccine types (5)

A
  • whole organism. live attenuated/inactivated
  • subunit. toxoid, antigenic extracts, recombinant proteins, conjugate vaccines
  • peptides
  • DNA vaccines
  • engineered virus
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2
Q

Describe the whole organism LIVE ATTENUATED vaccine type

A

pathogen altered to reduce virulence eg adaptation after prolonged cultivation on medium

  • organism is in a weakened form that can still replicate but at a v reduced rate
  • produces a short lived infection that the immune system can deal with without a harmful outcome
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3
Q

Describe the whole organism INACTIVATED vaccine type

A

organism is rendered inactive through heat/chemical treatment

  • can no longer replicate
  • designed to trigger innate response when exposed to danger eg LPS
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4
Q

Give an example of a live attenuated vaccine and state how it is produced

A

eg BCG vaccine against TB (bacterial)

  • Mycobacterium bovis cultured on media containing bile salts for prolonged periods of time (first time BCG vaccine created, grown for 13 years)
  • results in genetic changes of the organism to adapt to new medium
  • when placed in host cells (with different conditions) the BCG can no longer surivive because mutated therefore reduced virulence
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5
Q

Give examples of Whole Organism vaccines against both bacteria and viruses and state whether live attenuated (LA) or inactivated (IN)

A

Bacteria;
TB - BCG (LA)
Anthrax - (IN)
Cholera (IN)

Viral; 
Hep A (IN) 
Influenza (IN) 
Measles (LA) 
Mumps (LA) 
Polio Sabin (LA)
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6
Q

Describe the method of attenuating the polio Sabin pathogen and state when polio can cause disease

A

Polio virus grown on monkey kidney epithelial cells
Prolonged culture leads to adaptation and a strain that has reduced virulence in humans
Can cause an outbreak if fall in sewage system.

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7
Q

What are the 5 advantages of a live attenuated vaccine?

A
  • get a transient infection
  • full activation of the immune response
  • generation of memory B T cells resulting in prolonged and comprehensive protection
  • prolonged contact with the immune system
  • as the vaccine can replicate, antigen released over a period of time. in contrast to single vaccination with antigenic extracts or inactivated organism so only single immunisation required (+Ves in the 3rd world)
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8
Q

What are the 3 disadvantages of live attenuated vaccine giving some examples

A
  • immunocompromised individuals may become infected as a result of immunisation
  • post immunisation complications although rare may exist eg some may be hypersensitive. everyone’s immune response is different

eg polio Sabin around 1 in 2,400,000 will revert back to original pathogenic form. in areas with poor sanitation this can lead to serious outbreak there polio Salk (inactivated) normally used
eg live measles vaccine. 1 in 1,000,000 post infectious encephalomyelitis (normally around 1 in 1000 with natural disease)

  • Refrigeration and transport - LA vaccines require stable transport. may be hard for remote countries.
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9
Q

What are the 3 advantages of a WHOLE INACTIVATED organism vaccine?

A
  • many different antigenic components so good IR possible
  • no risk of infection
  • storage and transport less of an issue
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10
Q

What are the disadvantages of a WHOLE INACTIVATED organism vaccine?

A
  • tend to just activate humeral responses. no T cell response
  • without transient infection, the IR can be quite weak therefore booster injections required. patient compliance needed for patients to return for their boosters
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11
Q

How can whole inactivated organisms be improved even though they cause no transient infection?

A

adjuvants can be used to improve IR

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12
Q

give an example of when an activation procedure went wrong, what is the normal inactivation procedure for this example?

A

polio Salk vaccine in the 50s was incorrectly inactivated. causing a series of outbreaks.
polio Salk normally inactivated through chemical treatment with formaldehyde

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13
Q

When inactivating a pathogen, what also needs to be ensured so that we get a proper immunogenic response

A

treatment doesn’t reduce immunogenicity of antigen. need to ensure correct response

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14
Q

What modern approaches can be used to inactivate an organism for a vaccine?

A

DNA recombinant technology used to remove genes for virulence and NOT remove genes invovled in establishing infection

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15
Q

Give bacterial/viral inactivated vaccine examples

A

BACTERIAL;
- anthrax, cholera
VIRAL;
- Hep A, influenza, polio Salk

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16
Q

Sum up what subunit vaccines are v BRIEFLY

A
  • purify molecular components as immunogenic agents
  • no risk of infection
  • theoretically safer than handling live/inactivated pathogens
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17
Q

Briefly describe the 3 main types of subunit vaccine

A

INACTIVATED EXOTOXINS (toxoids);
- eg heating up of tetanus toxin or treating w/ formaldehyde so it retains its antigenicity but has no damaging effects
CAPSULAR POLYSACCHARIDES;
- repeating structures that can be easily recognised therefore v antigenic
RECOMBINANT MICROBIAL ANTIGENS;
- express these antigens then purify them

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18
Q

Name 2 bacterial exotoxins that toxoids can be created from and describe them

A 
DIPHTHERIA TOXIN; 
inactivates mammalian elongation factor (EF2) 
inhibitor of translation 
lethal dose 10ng/kg 
leading to necrosis of liver and heart

TETANUS TOXIN;
neurotoxin
uncontrolled contraction of voluntary muscles

19
Q

What is a toxoid?

A

toxin that has been treated (w/ heat/chemically) to reduce its toxicity

20
Q

What are capsular polysaccharides and what is the importance of them?

A

highly polar, hydrophilic cell surface polymers that consist of oligosaccharide repeating units
main antigens invovled in protective immunity to encapsulated bacteria
important in interfering with phagocyte interactions w/ bacteria. block opsonisation of the pathogen by complement and Abs therefore preventing phagocytosis and destruction of the bacteria

21
Q

What are recombinant proteins in terms of developing a subunit vaccine?
Give an example

A

clone and express a single gene in a host
eg subunit vaccine of Hep B surface proteins cloned and expressed in yeast
eg Gardasil. subunit vaccine for HPV. virus coat proteins expressed in yeast and assemble in virus - like particles

22
Q

why are conjugate vaccines useful?

A

sometimes the target antigen (eg capsular polysaccharide) may only stimulate a weak T cell response. this would reduce the induction of immunological memory.
(true for other antigens, because of their 3D shape would only give a good B cell response)
overcoming this, the powerful antigen (ie in this case capsular polysaccharide) can be chemically conjugated to a 2nd antigen (can be but not limited to being from the same organism)
immunisation can therefore stimulate both B/T cell responses and generate T/B memory cells
HOWEVER THIS FIELD ADVANCING V SLOWLY

23
Q

how are synthetic peptides being used as vaccines? Draw a diagram to explain your answer

A

want to produce a peptide that has immunodominant B cell epitopes and can stimulate memory T cell responses
311 - 16 word

24
Q

What are the difficulties in manipulating certain peptides to be used as vaccines?

A
  • HLA genes and MHC presentation of peptides is essential therefore response to peptides is HLA dependent. may be different in certain individuals
  • B cell epitopes are conformational
  • peptides can be stimulatory or suppressive
25
Q

What are the advantages of subunit vaccines?

A
  • safety, no risk of infection as only portion of the pathogen used
  • may be easier to store and preserve
26
Q

What are the disadvantages of subunit vaccines?

A
  • immune response less powerful to live attenuated vaccines
  • booster/repeat vaccinations and adjuvants required to give sufficient immune response
  • subunits chosen have to illicit a wide range of responses in a no. subjects (HLA differences). need to give broad response in most people
27
Q

What are adjuvants?

A

essentially any substance added to a vaccine that is designed to trigger the IS.
act as a delivery system and immune stimulators
- more specifically triggering the innate IS and telling the body it has an infection

28
Q

Give examples of vaccines that can include adjuvants

A
  • whole killed organism
  • toxoid
  • proteins (conjugate vaccines)
  • chemicals (Al salts, oil emulsions)
29
Q

Describe why Al salts and oil emulsions can be used as adjuvants

A

Al salts;
Al chelates to the antigen. sits at the body at the site of infection and is slowly released over time @ the point of injection.
extends the half life of the immunogen (prolongs the danger signals)

Oil emulsion;
irritant, initially stimulating innate IS and inflammation

30
Q

___ and ___ ___ trigger the immune system and send out danger signals

A

toxoids

killed organisms

31
Q

What part of the immune system do adjuvants tend to trigger?

A

innate IS
leading to improved Antigen presentation to immune cells. links to adaptive response.
as they invovle PAMPs/DAMPs they trigger PRRs eg TLRs

32
Q

Give 2 more examples of agonists apart from Al salts and oil/water emulsions

A

TLR agonists

detoxified bacterial LPS

33
Q

Even though they are highly efficient there are a number of safety hazards associated, what are they?

A

risk of autoimmunity

chronic inflammation

34
Q

What is the aim of DNA vaccines?

A

to transiently express genes from pathogens in host cells. generating an IR(similar to natural infection) including T B cell response -> immunological memory

35
Q

Draw a diagram summarising DNA vaccines

A

311 - 16 word

36
Q

What has been done to prove DNA vaccination?

A

no. animals injected with genes from a variety of infectious agents from HIV, Rabies, Influenza, Hep B
some protective responses have occurred

37
Q

Why can DNA vaccines be used currently?

A

too little is known still about how DNA vaccines lead to an immune response

  • we could get individuals raising Ab to DNA (anti-DNA) REALLY do not want this
  • any possible side effects we dont yet know about?
38
Q

What are the advantages of DNA vaccines?

A
  • do not require complex storage and transportation

- administered easily ie in a DNA gun. therefore can be adapted to widespread vaccination programmes

39
Q

What are the disadvantages of DNA vaccines?

A
  • as with killed and subunit vaccines no transient infection. DNA does not last long and is broken down
  • immune response is mild therefore booster injections required
  • could get immune responses to DNA?
  • no current DNA vaccines for human use. although is DNA vaccine for horses in response to West NILE VIRUS
40
Q

What are the aims of recombinant vector vaccines? And briefly describe them

A
  • imitate the effects of transient infection of a pathogen but using a non-pathogenic organism
  • genes for the pathogenic antigens introduced into the non-pathogenic/attenuated organism. then introduced into the host
41
Q

give examples of recombinant vector vaccines

A

both bacterial/viral

  • canary pox, attenuated poliovirus
  • attenuates Salmonella strains, BCG strain of M. Boris
42
Q

What are some examples of recombinant viral vaccines

A

adenovirus - strains that can infect humans

vesicular stomatitis virus - relative of rabies virus

43
Q

What are the +ves/-ves of recombinant viral vaccines?

A

+ves;

  • safe - relative to live attenuated pathogen
  • immunological memory
  • creates ideal stimulus to IS
  • flexible - different components can be engineered in
  • ves;
  • cause illness in compromised people
  • immune response to the virus can negate effectiveness
  • refrigeration for transport
44
Q

What are the key constituents of an ideal vaccine?

A
  • Safe; this could mean attenuated live if suitable or subunit if the pathogen is lethal for example
  • Should induce a suitable immune response; for example mucosal if pathogen uses this route, high antibody titer if antibody most useful protective agent
  • Generate T and B cell memory
  • Stable and easy to transport for use in remote areas
  • Should not require repeated boosting; patient compliance

311 - Molecular Immunology (18 decks)

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