Lecture 24 Viral Vaccines Flashcards
What is a vaccine?
How does a vaccine act?
- 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
What are the different types of vaccines? (6)
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
what is the most common vaccine - why?
- live attenuated vaccine
- they are the virus that is attenuated (weakened)
- closest thing to the real virus
- evokes strong innate and adaptive immunity
Describe the 3 eras that lead to eradication of smallpox
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
what are the features of small pox that enabled its eradication from a
virology and disease point:
an immunological point:
a social-political point:
- 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
what wild type strain of polio is present still
polio strain 1
what is the Sabin vaccine
how is it taken
how is is made
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)
what is the salk vaccine
how is it taken
how is it made
polio inactivated virus
injection
formalin is used to inactivate virus
first polio vaccine made
what are the main differences between salk and sabin vaccine
what are the similarities
- 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
How many mutations are in the vaccine for the sabin vaccine - for each strain?
Strain 1 - 5 aa mutations
Strain 2 - 2 aa mutations
Strain 3 - only 1 aa mutation in the VP3 region
Why can the type 3 sabin vaccine revert to virulence?
- because the vaccine virus only has one aa mutation
- over time it can revert back to virulence
where do you use the sabin vaccine vs. the salk vaccine?
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
what type of vaccine is the measles vaccine
live attenuated
what does the measles vaccine protect from
acute measles and chronic measles (SSPE)
what are 3 pros and 4 cons of live attenuated vaccines?
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
what are the new approaches to viral vaccines
viral vectors DNA vaccines Targeting strategies VLPs live attenuated re-assortant vaccines
what is the most used virus for vaccine virus vectors?
Vaccinia (poxvirus) - large DNA virus
How do you make a virus vector vaccine / how does it work
- 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
How do you make a vaccinia virus vector vaccine?
- 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
what are the advantages and disadvantages of virus vector vaccines
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
what diseases currently use viral vector vaccines
- Ebola
- Japanese encephalitis
- Dengue
how do are VLP vaccines made
what vaccines use this
- 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
how is the Hep. B vaccine made?
- 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
What is the gardasil vaccine and what does it protect against
- 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
how can you use targeting strategies for vaccines
- 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
How are live attenuated reassortant vaccines made
- 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
what virus do we use a live attenuated reassortant vaccine for?
Influenza - called flumist
