Approaches To Vaccinations To Prevent Viral Infection And Disease Flashcards
Why vaccinate?
To prevent spread of the pathogen, prevent infection
To prevent serious disease
What are the 2 different vaccines for polio?
Oral (live attenuated)
Inactivated (killed vaccine)
What are the methods of production of live attenuated vaccines?
Viruses passaged in cell culture or non-human mammals
Closely related viruses isolated from other non-human species
Genetically engineered attenuations
What diseases have live attenuated vaccines?
Measles, mumps, rubella
Yellow fever
Oral polio vaccine (Sabin)
What is variola virus also known as?
Small pox
What can polio cause?
Acute paralysis (hours of infection)
What are the three distinct sterotypes of poliovirus?
PV1, PV2, PV3
What does the IPV vaccine for polio do?
Is killed inactivated, gives you a good systemic immunity, good IgG response but as it is an enterovirus, it gets into body orally so need a good IgA response
What does the liver attenuated poliovirus do?
Gives good sterilising immunity
Replicating in your gut, gets into sewers, unvaccinated people drink that water and may get vaccinated without knowing
Quickly become pathogenic, now have vaccine derived polio 1,2,3
What are the two names of the polio viruses?
Salk - killed inactivated
Sabin - live attenuated
How did the Sabin vaccine revert to pathogenicity?
Single point mutation in type 2 polio Sabin vaccine strain permits reversion to paralytic phenotype
Where was the mutation in Sabin vaccine strain?
5’ UTR
What is different about nOPV2?
Introduced 15 point mutations, genetic barrier to reversion is much higher
Benefits of live attenuated?
Longer period of immune activation
Provides more natural immunity
Correct antigen presentation
Cheaper
Quicker to generate large stocks
What are limitations of live attenuated vaccines?
Can cause mild disease
Vaccinee can transmit the vaccine
Immunocompromised individuals - potentially harmful
Can revert to pathogenicity
Unstable
How are killed vaccines generated?
Typically chemical inactivation
Grow virus and supernatant
Get rid of heavy stuff
Put it over a cushion (lots of sucrose), sugar get forced down through liquid, then spin under cushion
End up with a virus pellet which you can resuspend
Put them in an adjuvant
What is the HepA virus vaccine that was discontinued?
Havrix
Killed vaccine benefits
Quick, cheap
Longer period of immune activation
Contains all antigens
Provides natural immunity
Drawbacks for killed vaccines
Process can denature antigens
No virus shedding - no passive immunisation
Potentially harmful for immunocompromised individuals
Requires adjuvant
Unstable
What do subunit vaccines typically contain?
A single recombinantly expressed viral protein
What is the HBV vaccine like?
Both comprise recombinantly expressed surface glycoprotein
Monomeric does not induce a protective immune response
Protein spontaneously self-assembles in virus-like particles
What do two HBV vaccines differ in?
In concentration of the HBsAg and nature of adjuvant
What is the problem with HepB vaccine?
Need a least 3 and most people haven’t seroconversion so need another one
What are the 3 N terminal variants for HBV vaccine?
HBsAgL
HBsAgM
HBsAgS
What types of HBV vaccines are present in mature infectious particles?
L and S
What is Mosquirix?
The first licensed human parasite vaccine
- non-infections virus like particles produced in yeast cells by recombinant DNA technology
What are the 3 elements of mosquirix?
A fusion protein
Native hepatitis B surface antigen
AS01E adjuvant
What can mosquirix immunise against?
Malaria and HBV
Sub unit vaccines pros?
Select highly antigenic regions
Pure, very safe
No chance of reversion
Suitable for more vulnerable groups
Good humoral response
Limitations of subunit vaccines?
Low immunogenicity
Expensive
Antigen presentation may differ from native form
Limited cell-mediated response
Unlikely to prevent transmission
What do viral vector vaccines do>
Non-pathogenic viral vectors express proteins from target pathogen
- antibody response generated to protein of interest and components of the viral vector
What is MVA?
Modified vaccinia virus Ankara
What is MVA vaccine structure
Enveloped dsDNA virus
What is VSV
Recombinant vesicular stomatitis virus (rVSV)
What is structure of VSV?
Enveloped (-) ssRNA virus
How does VSV vector work as a vaccine?
Replace the VSVg gene with GP of virus of interest
Why can’t you use human adenovirus vector?
Already have good anitbodies against it so need one we have no encountered before
What is used instead of human adenoviruses as a vector?
Chimp AdV
Why are adenoviruses good?
Genetically stable, non enveloped
DsDNA, not integrating or mutating
Why is getting into dendritic cells good for adenovirus vectors?
Because they are good antigen presenting cells for MHC class 1 and 2
What type of vaccine is Oxford AstraZeneca?
Recombinant genome encodes unmodified S glycoprotein of SARS-CoV-2
Immunogen is expressed in the stable, trimeric, perfusion conformation
What does expression cassette of AstraZeneca include?
S protein expressed with an N-terminal fusion to the tissue plasminogen activator leader/signal peptide
Modified human cytomegalovirus promoter
Bovine growth hormone polyadenylation sequence
Viral vector vaccines pros
Established production pipelines
Quicker regulatory process - same platform can be applied to multiple targets
Limitations of viral vector vaccines
Results in strong immune response to vector antigens
Prime-boost strategies increase cost
What is aim of mRNA vaccines?
Achieve expression of antigens within cells
- MHC class I presentation - all nucleated cells
- MHC class II presentation is preferred - dendritic cells
What do all mRNA vaccines contain?
Encode 1 or more antigens
5’ cap
3’ poly-A tail
What is the challenge with mRNA vaccines?
MRNA is a strong PAMP
What are mRNA optimisations for vaccines?
Codon optimisation (improve translation efficiency)
Purification techniques (remove dsRNA)
Modified nucleosides (prevent endosomal TLR recognition)
Encode additional genes
What is Moderna vaccine?
Intramuscular mRNA vaccine
- 5’ capped mRNA produced using a cell-free in vitro trnscpirotn from corresponding DNA templates, encoding viral spike protein of SARS-CoV-2
What is monovalent v bivalent for Moderna?
Monovalent initially - viral spike protein of SARS-CoV-2
Bi-valent more recently - 50:50, original spike sequence, omicron BA.1, BA4-5
What are mRNA pros?
Platform can be used repeatedly for different diseases (no ‘vector’ immunity)
Rapid addition of new variant strain antigens to vaccine mix
Elicits good systemic T and B cell responses
Relatively cheap and quick to produce
What are mRNA negatives
Optimisation disagreement
Storage is not ideal
Delivery/adjuvant system disagreement
Limited mucosal Ab response in naive vaccines
How does mRNA vaccines trigger B cell responses
Dendritic cell takes up mRNA
Produces antigen and presents on MHC1/2
T cells recruited and activated
CD4+ T cell recognises epitope ‘XYZ’
Circulating B cell recognises SARS-CoV-2 coat protein via epitope ABC
B cell internalises virion and digests it
Activated CD4+ cell recognises cognate antigen and activates B cell
What are DNA vaccines?
DNA containing antigenic coding region plus promoters
What is main challenge of DNA vaccines?
Method of administration
What is the issue with passive vaccines?
Offers immediate but short-lived immunity
What are passive vaccines commonly used for?
HBV and rabies
What is adoptive transfer?
Administration of stimulated cells
- longer lasting than just IgG due to increased half-life of T-cells compared IgG
What are the dengue virus issues?
No validated correlates of protection
4 serotypes
Antibody dependent enhancement means second infection can be fatal
Researchers and officials facing criminal charges in phillipines due to failed vaccine
