Lecture 24 Viral Vaccines Flashcards

1
Q

What is a vaccine?

How does a vaccine act?

A
  • vaccine is derived from a pathogen
  • it does not cause disease in the host but it induces protective immunity in the host
  • it acts as the initial infection
  • it primes the immune response to the antigens of a pathogen
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2
Q

What are the different types of vaccines? (6)

A

Live attenuated vaccine - weakened live virus
Inactivated vaccine - inactivated with chemicals
fractionated vaccine - purify an antigen to make a vaccine with
plasmid DNA vaccine
Virus Vector vaccine
Virus like particle vaccine

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3
Q

what is the most common vaccine - why?

A
  • live attenuated vaccine
  • they are the virus that is attenuated (weakened)
  • closest thing to the real virus
  • evokes strong innate and adaptive immunity
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4
Q

Describe the 3 eras that lead to eradication of smallpox

A

Pre-jenner
- variolation innoculation - pustule from smallpox was ground up and used in cuts and put up nose to vaccinate people
death rate was alot lower than virus death rate

Jenner period

  • Jenner realised that cowpox protected from smallpox
  • cowpox causes mild infection in humans as we are not the natural host
  • cowpox was initially passaged in humans but had issues with transmission of hep. c and syphillis so started passaging in cows

Post Jenner era

  • vaccinia virus replaced cowpox for vaccination
  • still provides immunity and works as a vaccine
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5
Q

what are the features of small pox that enabled its eradication from a
virology and disease point:
an immunological point:
a social-political point:

A
  • no secondary hosts - only present in humans
  • long incubation period
  • infectious only when pustules are present - not infectious if asymptomatic
  • low communicability
  • not a persistant infection
  • easily diagnosed
  • immunity generated is long term
  • there is only one serotype
  • vaccine available and its cheap
  • it was a disease with high morbidity and mortality therefore people wanted to eradicate it
  • savings from eradicating the virus
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6
Q

what wild type strain of polio is present still

A

polio strain 1

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7
Q

what is the Sabin vaccine
how is it taken
how is is made

A

polio live attenuated vaccine
oral
passaged through monkey kidney cells repetitively - the virus will adapt to the monkey kidney cells and will no longer be able to infect human cells (becomes attenuated)

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8
Q

what is the salk vaccine
how is it taken
how is it made

A

polio inactivated virus
injection
formalin is used to inactivate virus
first polio vaccine made

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9
Q

what are the main differences between salk and sabin vaccine

what are the similarities

A
  • Salk does not produce mucosal immunity (IgA)
  • Sabin produces nasal IgA and duodenal IgA which is important against polio infection
  • They both produce a robust immune response - induces serum IgM and IgG
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10
Q

How many mutations are in the vaccine for the sabin vaccine - for each strain?

A

Strain 1 - 5 aa mutations
Strain 2 - 2 aa mutations
Strain 3 - only 1 aa mutation in the VP3 region

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11
Q

Why can the type 3 sabin vaccine revert to virulence?

A
  • because the vaccine virus only has one aa mutation

- over time it can revert back to virulence

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12
Q

where do you use the sabin vaccine vs. the salk vaccine?

A

sabin is used in places where mucosal immunity is needed i.e. endemic places like africa
salk is used in places that have virtually eradicated the virus

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13
Q

what type of vaccine is the measles vaccine

A

live attenuated

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14
Q

what does the measles vaccine protect from

A

acute measles and chronic measles (SSPE)

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15
Q

what are 3 pros and 4 cons of live attenuated vaccines?

A

pros

  • few doses required
  • long lasting immunity
  • similar type of immune response as to the pathogen itself

Cons

  • may need booster dose
  • cannot use in immunocompromised - they will succumb to infection
  • can be shed into environment as it is a live virus - other people can pick it up and succumb to infection
  • potential to revert back to virulence
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16
Q

what are the new approaches to viral vaccines

A
viral vectors
DNA vaccines
Targeting strategies 
VLPs 
live attenuated re-assortant vaccines
17
Q

what is the most used virus for vaccine virus vectors?

A

Vaccinia (poxvirus) - large DNA virus

18
Q

How do you make a virus vector vaccine / how does it work

A
  • add the virus vaccine gene into an attenuated viral vector
  • vector may cause a mild infection in host
  • vaccine antigen will be expressed in the host
19
Q

How do you make a vaccinia virus vector vaccine?

A
  • construct a plasmid containing vaccinia genome and the vaccinia thymidine kinase (TK) gene
  • insert an early promoter in the centre of the TK gene to disrupt it
  • downstream from the promotor insert the vaccine gene of interest i.e. influenza HA gene
  • then place the plasmid into a cell along with a wild-type vaccinia virus containing a functional TK gene
  • due to homologous recombination the mutated gene will insert into the WT vaccinia
  • this makes a vaccinia virus that is defective as it has a defective TK gene and it contains the vaccine Ag
    (vaccinia is attenuated without the TK gene)
  • delete all the thymidine positive viruses
  • attenuated virus can now be administered into person
20
Q

what are the advantages and disadvantages of virus vector vaccines

A

advantages

  • high levels of vaccine antigen expressed
  • can be delivered by mucosal route
  • can ilicit CTL and Ab response

cons

  • cannot be used in immunocompromised
  • may be an immune response against the virus vector
21
Q

what diseases currently use viral vector vaccines

A
  • Ebola
  • Japanese encephalitis
  • Dengue
22
Q

how do are VLP vaccines made

what vaccines use this

A
  • some virus capsids or envelope proteins can self assemble
  • to form VLPs
  • they look exactly like the virus - but they are empty
  • Hep. B vaccine uses HbsAg
  • HPV uses Rec L1 capsid protein
23
Q

how is the Hep. B vaccine made?

A
  • Hep B vaccine is a VLP vaccine of the HbsAg
  • made in yeast
  • HbsAg is put into a vector - put in yeast - vector will produce HbsAg - the HbsAg will make VLPs which will be used for vaccine
24
Q

What is the gardasil vaccine and what does it protect against

A
  • VLP vaccine for HPV
  • VLPs are made from the Rec L1 capsid protein
  • made in yeast
  • protects against 7/10 cancer causing HPVs and 9/10 cases of genital warts
  • vaccine elicits a much greater response than what the natural infection does
25
Q

how can you use targeting strategies for vaccines

A
  • use a molecule that binds to a receptor on immune cells to target the immune cells
  • can use these molecules to target recombinant proteins or proteins expressed from DNA vaccines to relevant sites
  • targeting approches can lead to maturation of the DC and promote peptide loading
26
Q

How are live attenuated reassortant vaccines made

A
  • made with 2 viruses with segmented genomes i.e influenza
  • the parent viruses are: a virulent virus with the vaccine antigen added to it / and a non-pathogenic/weak strain
  • they will reassort and will end up with a non-pathogenic virus strain with the viral vaccine Ag inserted
27
Q

what virus do we use a live attenuated reassortant vaccine for?

A

Influenza - called flumist