4-5: Vaccines Flashcards
passive vs. active immunisations
passive is just the transfer of antibodies (maternal, etc.)
- IgG from placenta and IgA from breastmilk
active is usually vaccines
- establish memory with active immunisation
passive immunisation
transfer of antibodies
immune protection lasts as long as antibodies are present
does not establish memory
- IgA from breastmilk in digestive track but not blood
examples
- antitoxin (antibodies from horses immunised with toxin)
- human gamma globulin shots (human IgG from donors with many broad antibodies to pathogens)
how do vaccines work to provide active immunisation?
active immunisations inducing adaptive immune response similar to immunity/immune memory from a natural infection
provide protection by establishing memory T and B cells
- prevent disease but not infection
preventive vs. therapeutic vaccines
preventive
- protection against primary infection and disease
- usually given before exposure
therapeutic
- given to infected/exposed individuals to prevent/reduce disease or stimulate anti-tumour response
why the smallpox eradication was the case for vaccine success
no animal reservoir (just in humans)
lifelong immunity from infection/vaccination
one serotype
- little antigenic variation
- no repeat infections
effective attenuated vaccine
vaccination routes
mostly intramuscular or subcutaneous
- easiest place to inject but not the greatest immune mechanism
oral vaccines
- live polio and rotavirus
intradermal (between layers of skin)
- way to slowly release antigens
adjuvants
help increase inflammation, increase innate immune responses and increase immunogenicity
increased immunogenicity means more help to bind TLRs, more inflammatory responses, and more activation of macs and DCs
some vaccines are just proteins which means there’s no adaptive immune response
newer adjuvants (AS01-AS06)
have PAMPs which activate inflammation with TLRs
antigenic variation
viruses with many antigenic subtypes and high mutation rates
different viruses circulating at the same time
attenuated/live vaccines
live replicating or replication defect (which prevents it from causing more disease in people)
made by growing pathogen in non-human cell culture system until the pathogen is less virulent in human cells
- now made with recombinant DNA technology
low levels or slow replication
- idea that the immune system can get ahead of the virus with slow viral replication
advantages of attenuated/live vaccines
very successful (e.g. polio, measles)
self-replicating so low dose and non adjuvant
authentic antigen presentation
more effective to elicit CTLs
disadvantages of attenuated/live vaccines
if it replicates, it can infect other people and mutate to a virulent strain (reverse attenuation)
doesn’t deal with strain variability/antigenic variation
inactivated vaccines
killed/inactivated organisms/toxins
- inactivated with heat, chemicals, irradiation, etc.
inactivated toxin called a toxoid
advantages of inactivated vaccines
no revirulence (higher safety)
disadvantages of inactivated vaccines
no replication of pathogens
poor antigen presentation for CTLs
- will need constant boosters
live vector vaccines
use of vaccinia as a vector to deliver a piece of RNA or DNA
- recombination with a gene from the pathogen
insert genes from pathogen into a well-characterised vaccine vector
advantages of live vector vaccines
self-replicating with no adjuvant
disadvantages of live vector vaccines
issue with possible pathogenesis
ebola vaccine
live vector vaccine
taking innocuous cow virus, sticking it in a gene from ebola (RNA virus)
virus infects cells but cannot cause disease
- production of antigen from surface protein
live virus with no adjuvant and own PAMPs causing inflammation
recombinant protein vaccines
identifying immunogenic proteins and producing large quantities for immunisation
advantages of recombinant protein vaccines
potentially less expensive production and very safe
disadvantages of recombinant protein vaccines
only protein means no replication of the pathogen
- need adjuvants and boosters
- potentially no long-term memory
HPV vaccine
recombinant protein vaccine
vaccinia to express HPV capsid proteins which create virus-like particles (VLPs) to mimic virus structure
- VLPs have no HPV viral DNA
protein creates VLP which has no genome
- VLP fakes looking like a virus so the immune system treats it like a virus
3 immunisations with VLPs and adjuvants
- with no viral DNA, no PAMP so you need this
issues with vaccine efficacy
efficacy as how well the vaccine protects the immunised population
- most are >90% protective but influenza is 20-70% protective
potential different efficacy in adults vs. children or immunocompetent vs. immunocompromised individuals
issues with vaccine cost
number of people vaccinated vs. cost to manufacture
most original attenuated vaccines cheap
- incredible EOS
SARS vaccines
most of them using the spike protein as the main antigen
- few have the whole virus
spike protein is very large which makes it a great antigen
different types of vaccines
live attenuated
whole inactivated
split inactivated
synthetic peptides
virus-like particles
DNA/RNA
recombinant subunits
recombinant bacterial vectors
recombinant viral vectors
vaccine components
active ingredient
- mRNA containing spike protein gene (like in SARS)
adjuvants
- mRNA doesn’t have adjuvants but is in a lipid
- take out the RNA which encodes for the spike, put it into the RNA vector and surround it with a lipid (liposome)
stabilisers
- sugars added to the component put inside
- outside liposome to keep RNA and lipid stable (makes sure it doesn’t break down)
moderna vs. pfizer
both have mRNA inside lipid nanoparticles but different mRNA constructs with different lipid compositions
moderna has full-length spike protein
- pfizer only had part of the spike initially but now has the full-length
- different microgram doses
