Scientific Bases of vaccines Flashcards
Define vaccine?
Biological substance that does not cause disease and when administered to patient , an adaptive immune response is produced providing protection against future diseases
What is the overall immune response from MHC class 2?
Antigen taken in by endocytosis, peptide presented and naive CD4+ T cell binds to peptide MHc complex. CD4+ T cell becomes mature helper T cell (Th1 or Th2) and goes onto activate B cells to produce antibodies, or become memory helper T cell
What is the overall immune response from MHC class 1?
Antigen already inside cell (infection) , peptide presented and naive CD8+ T cell binds to peptide MHc complex. CD8+ T cell becomes mature CYTOTOXIC T cell (CTL) which kill infected cells using perforin+granzymes or become memory cytotoxic T cells
Define variolation?
Deliberate infection with smallpox - Jenner did with cowpox
What is the purpose of vaccinations?
Protect individual
Protect population - herd immunity
Eradicate disease (e.g. smallpox and almost polio)
What things in a vaccination need to be tested when being developed?
Challenge dose - prove protection from infection
Attenuation (reduced effect)
Prior exposure
Cross-species protection - antigenic similarity
What is the vaccine paradox?
Herd immunity = memory boosted. Used to be natural boosting by outbreaks f disease. Disease rates decline due to vaccinations but no more natural boosting so important of vaccine uptake increases
Why are vaccines taken despite side effects in some cases?
Better than acc infection conseqeunces
What is the immune response to a vaccination step by step?
Primary exposure - vaccination - antibody response, takes almost 2 weeks for class switching from IgM to IgG to take place. Memory B cells and Memory T cells made
Secondary exposure - real life - less than 7 days for response due to priot exposure
Why can all vaccines not be made in similair way? e.g.oral vaccine
Vaccine must induce correct TYPE of response e.g. antibodies, or cell medaited immunity, as well as in the RIGHT PLACE e.g. sIgA in mucosal membrane against influenza
How do duration of protection of vaccines cary?
Antibodies made are enough for short term
If long term, need memory, boosters needed (either naturally or via vaccine)
What is a incubation time and how does it vary?
Incubation time is how long it takes until you are actually protected from a disease due to pathogen after taking the vaccine - not immediately immune to pathoegen
Long incubation time - measles vaccine
Short incubation time - cholera vaccine
Why are vaccinations not given to neonates?
Already have maternal IgG antibodies through placenta and sIgA from breast milk. These antibodies might interfere with vaccine effects
- timings for diff vaccine vary
What is monotypic? and why is this important in vaccinations?
Surface antigens of pathogens stay unchanged e.g. measles virus
- only need one vaccine/infection - gives life long immunity
What is polytypic and how does this factor affect vaccinations?
Surface antigens change so immunity is readily overcome e.g. inflienza virus
need more than one vaccine
Define antigenic drift?
Accumulation of mutations in genes that code for surface proteins change with time
What is antigenic shift?
Recombination of several viral strains to produce a different subtype with a mixture of surface antigens from the original strains
What are the 3 types of vaccines?
live attenuated
Killed, whole organisms
Sub unity vaccine (individual components)
Give a examples of live attenuated vaccines?
Polio, MMR, yellow fever
How are attentuated forms of viruses/bacteria created? 3 ways
- Serial culture of host who had wild virus ages ago and carried attenuated version (measles)
- Chemical mutagenesis and selection of phenotypes
- genetic engineering to create knockouts lacking genes of virulence
Which cells are produced after live attentuated vaccine is administered?
Cytotoxic memory cells that can infect APCs
How are live attentuated vaccines stored?
Cold chain (refridgeration) to keep them alive- costs high
How are organisms killed for killed (inactivated) whole organisms vaccines?
using heat or chemicals e.g. formalin or B propiolactone used to inactivate influenza or pertussis
What is a requirement of killed whole organisms vaccine administrations?
Multiple doses to keep immunity at protective levels
Why does live attentuated vaccine not need multiple doses?
Natural boosting +much stronger responses so multiple doses not needed
What can be used for sub unit vaccines?
Protein e.g. surface antigens
Toxoids e.g for diptheria
Synthetic peptides
Polysaccharides (poor antigens) so conjugated to toxoids or outer membrane protein for strong enough response
How are toxoids made?
Inactivate toxins using formaldeyde
How do bacterial toxins provide immunity step wise?
Toxin inactivate into otxoids and used as vaccine allows cells to produce antibodies without tissue damage or disease from direct toxin itself
- antibodies produced = protection
How are bacterial capsular polysaccharides used as vaccines?
Much less immunogenic in children under 2 since they are poor antigens, have short term memory and have no T cell immunity
How are bacterial capsular polysaccharides made to be better vaccines?
Since they are short lasting, enhance immunogenicitiy via protein conjugation allowing long lasting immunity and response in children
Why do conjugated polysaccharides produce stronger immune response in children?
Not only do conjugated polysaccharides allow antibody production but the entire complex is taken up by cell (due to the protein) and presented on MHC class 2 of B CELLS allowing stronger immune response as well as antibody response
What are vaccine adjuvants?
Chemicals added to make vaccine more immunogenic
What is the purpose of vaccine adjuvants?
Enhance immune response to antigen (more antibodies produced)
promote uptake and antigen presentation
stimulate correct cytokine profile
Give an example of a vaccine adjuvant? and how does it work)
Aluminium salts (allow slow release of antigen)
What are the difficulties in producing vaccine against HIV?
High mutation rate - immunity against one strain would be ineffective
Effective vaccine also needs to induce memory CTLs so needs to be live attentuated vaccine - danger of reversion to virulence!!! esp due to the high mutation rate
Why are live attentuated vaccine used?
Strong response and long term since produces CYTOTXIC CTL MEMORY CELLS
Why can’t some viruses be given as live attenutated vaccines + example?
Polio - can revert back to virulence
Disadvantages of live attentuated?
Cost for refridgeration
Possibiloty of conversion back to virulence
What is a passive immunity?
Treatment with antibody from another source e.g. serum
Give example of passive immunity?
maternal transfer
prophylaxis
Whatis the point of passive treatment?
Rapid short effect