16 - Types of Vaccines - Watson Flashcards
Name all the different vaccine types (5)
- whole organism. live attenuated/inactivated
- subunit. toxoid, antigenic extracts, recombinant proteins, conjugate vaccines
- peptides
- DNA vaccines
- engineered virus
Describe the whole organism LIVE ATTENUATED vaccine type
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
Describe the whole organism INACTIVATED vaccine type
organism is rendered inactive through heat/chemical treatment
- can no longer replicate
- designed to trigger innate response when exposed to danger eg LPS
Give an example of a live attenuated vaccine and state how it is produced
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
Give examples of Whole Organism vaccines against both bacteria and viruses and state whether live attenuated (LA) or inactivated (IN)
Bacteria;
TB - BCG (LA)
Anthrax - (IN)
Cholera (IN)
Viral; Hep A (IN) Influenza (IN) Measles (LA) Mumps (LA) Polio Sabin (LA)
Describe the method of attenuating the polio Sabin pathogen and state when polio can cause disease
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.
What are the 5 advantages of a live attenuated vaccine?
- 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)
What are the 3 disadvantages of live attenuated vaccine giving some examples
- 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.
What are the 3 advantages of a WHOLE INACTIVATED organism vaccine?
- many different antigenic components so good IR possible
- no risk of infection
- storage and transport less of an issue
What are the disadvantages of a WHOLE INACTIVATED organism vaccine?
- 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
How can whole inactivated organisms be improved even though they cause no transient infection?
adjuvants can be used to improve IR
give an example of when an activation procedure went wrong, what is the normal inactivation procedure for this example?
polio Salk vaccine in the 50s was incorrectly inactivated. causing a series of outbreaks.
polio Salk normally inactivated through chemical treatment with formaldehyde
When inactivating a pathogen, what also needs to be ensured so that we get a proper immunogenic response
treatment doesn’t reduce immunogenicity of antigen. need to ensure correct response
What modern approaches can be used to inactivate an organism for a vaccine?
DNA recombinant technology used to remove genes for virulence and NOT remove genes invovled in establishing infection
Give bacterial/viral inactivated vaccine examples
BACTERIAL;
- anthrax, cholera
VIRAL;
- Hep A, influenza, polio Salk
Sum up what subunit vaccines are v BRIEFLY
- purify molecular components as immunogenic agents
- no risk of infection
- theoretically safer than handling live/inactivated pathogens
Briefly describe the 3 main types of subunit vaccine
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
Name 2 bacterial exotoxins that toxoids can be created from and describe them
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
What is a toxoid?
toxin that has been treated (w/ heat/chemically) to reduce its toxicity
What are capsular polysaccharides and what is the importance of them?
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
What are recombinant proteins in terms of developing a subunit vaccine?
Give an example
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
why are conjugate vaccines useful?
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
how are synthetic peptides being used as vaccines? Draw a diagram to explain your answer
want to produce a peptide that has immunodominant B cell epitopes and can stimulate memory T cell responses
311 - 16 word
What are the difficulties in manipulating certain peptides to be used as vaccines?
- 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
What are the advantages of subunit vaccines?
- safety, no risk of infection as only portion of the pathogen used
- may be easier to store and preserve
What are the disadvantages of subunit vaccines?
- 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
What are adjuvants?
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
Give examples of vaccines that can include adjuvants
- whole killed organism
- toxoid
- proteins (conjugate vaccines)
- chemicals (Al salts, oil emulsions)
Describe why Al salts and oil emulsions can be used as adjuvants
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
___ and ___ ___ trigger the immune system and send out danger signals
toxoids
killed organisms
What part of the immune system do adjuvants tend to trigger?
innate IS
leading to improved Antigen presentation to immune cells. links to adaptive response.
as they invovle PAMPs/DAMPs they trigger PRRs eg TLRs
Give 2 more examples of agonists apart from Al salts and oil/water emulsions
TLR agonists
detoxified bacterial LPS
Even though they are highly efficient there are a number of safety hazards associated, what are they?
risk of autoimmunity
chronic inflammation
What is the aim of DNA vaccines?
to transiently express genes from pathogens in host cells. generating an IR(similar to natural infection) including T B cell response -> immunological memory
Draw a diagram summarising DNA vaccines
311 - 16 word
What has been done to prove DNA vaccination?
no. animals injected with genes from a variety of infectious agents from HIV, Rabies, Influenza, Hep B
some protective responses have occurred
Why can DNA vaccines be used currently?
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?
What are the advantages of DNA vaccines?
- do not require complex storage and transportation
- administered easily ie in a DNA gun. therefore can be adapted to widespread vaccination programmes
What are the disadvantages of DNA vaccines?
- 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
What are the aims of recombinant vector vaccines? And briefly describe them
- 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
give examples of recombinant vector vaccines
both bacterial/viral
- canary pox, attenuated poliovirus
- attenuates Salmonella strains, BCG strain of M. Boris
What are some examples of recombinant viral vaccines
adenovirus - strains that can infect humans
vesicular stomatitis virus - relative of rabies virus
What are the +ves/-ves of recombinant viral vaccines?
+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
What are the key constituents of an ideal vaccine?
- 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
