Vaccines Flashcards
before Edward Jenners discovery (cow pox for small pox) what was used for small pox inoculation in asia in the 1500s
ground up small pox scabs blown into the nostril or scratching matter from a sore
what did Thucydides notice in 430BC Athens
that survivors of the plague were resistant to further attacks of the plague but not to other diseases
what is immunisation
the process of eliciting a state of protective immunity against a disease causing pathogen
how was the covid-19 vaccine developed so fast
was tested on other types of sars
many years already contributing to platform (mRNA tech)
cost not a problem bcos every country contributed
no shortage of viable patients
phases were overlapped
didn’t wait to develop a batch method
give features of the ideal vaccine
- give lifelong immunity
- broadly protective against variants
- prevent disease transmission
- induce effective immunity rapidly
- be effective in all vaccinated subjects
- transmit maternal protection to foetus
- require few immunisation to induce protection
- not administered by injection
- affordable world wide
- stable (temp, no cold chain)
what 3 ways can passive immunity be acquired
naturally when maternal IgG crosses placenta
maternally produces IgA in breast milk
injection with preformed antibodies (antiserum)
what is passive immunity
immunity acquired without activation of hosts natural immune response
what is active immunity
immunity in which the hosts immune system plays an active role through antigen specific T and B cell activation and formation of protective memory cells
what two ways can active immunity be acquired
natural infection
and vaccinations
when is passive immunity used in treatments
- babies born with congenital immune deficiencies
- unvaccinated individual exposed to botulism tetanus diphtheria measles rabies (things that will have immediate effect if not treated)
- antiserum provides antidote against poisonous venom
- exposure to pathogen that causes death faster than immune response
what are the possible risks of passive immunity
host immune system can mount an anti isotype response if antibody is from another species - systemic anaphylaxis
activation of complement immune complexes through IgM or IgG - type 3 hypersensitivity reactions
what drug induced passive immunity against ebola
Zmapp (made of three humanised monoclonal antibodies harvested from mice exposed to ebola virus proteins)
what is the primary goal of vaccination
to offer long term protection by inducing a memory response
what is the principle of vaccination
to mimic infection in a way that activates host immune response in order to induce long lasting immunological memory
what cells are involved in the innate immune response
NK cells, mast cells, eosinophils, basophils, macrophages, neutrophils, dendritic cells
what are the steps to generating an immune response from vaccination
1 uptake of vaccine by phagocytes
2 activation and migration of APCs from infected tissue to peripheral lymphoid organs (closest to vac site)
3 antigen presentation to T and B cells
4 activation of T and B cells
5 long lasting protection through memory cell development
where does t cell activation occur
in secondary lymphoid organs (lymph nodes, spleen, peyers patches, mucosal tissues (adenoids and tonsils))
what 3 things are required for t cell activation
1 recognition of antigen by TCR
2 costimulatory signal between CD28 (on t cell) and CD80/86 (on apc)
3 cytokine mediated differentiation and expansion
what are the 4 types of memory t cell
stem cell memory t cells - in secondary lymphoid organs, give rise to central memory t cells
central - reside in 2ndary lymphoids
effector - circulate among tissues
resident - settle in peripheral tissues for a long time, first cells to respond to reinfection
what is immunological memory
the ability of the immune system to respond with greater vigour upon re ecounter with the same pathogen
why would vaccination not be 100% effective
incomplete uptake of boosters
small percentage may not respond
immune deficiency
poor uptake due to health scares
what is measles
a respiratory system infection caused by paramyxovirus via aerosol transmission
what is the MMR vaccine
a combined vaccine of measle mumps and rubella - live attenuated vaccine
what is herd immunity and when is it effective
immunity developed by a group of vaccinated individuals- immunised majority allow few unimmunised to be protected - effected when 80-95% are vaccinated (depends on disease)
what are the barriers to widespread coverage (herd immunity) in the developed world?
access and cost issues among certain populations
language barriers
failure to obtain booster shots/complete series
fears concerning vaccination
what are the barriers to widespread coverage (herd immunity) in the developing countries?
storage requirements poor infrastructure lack of roads personnel issues conflict
what components make up the newly film based vaccine
attenuated virus, methylcellulose, sugar alcohol and surfactant
what does the SARS-CoV2 virus bind to on the host target cell - what other protein is involved
ACE2 (binding to RBD motif of spike)
TMPRSS2 cleaves the spike to allow viral entry
what are the two main influenza antigens
Hemagglutinin (binds to host cell receptor)
Neuraminidase (clips polysaccharide chains from host cell surface, facilitate new viral particle release)
what are the types of influenza virus
Influenza A and B (related to seasonal epidemics) Influenza C (mild symptoms)
what mechanisms cause variations in influenza
antigenic drift (seasonal flus) antigenic shift (pandemics)
what is antigenic shift
re assortment of entire ssRNA between human and animal virons infecting the same cell - human antibodies have no recognition- drives pandemics
what is antigenic drift
accumulation of point mutations entail ly yielding a variant protein no longer recognised by the antibody to the original antigen - causes seasonal flu and covid variants
what is sterilising immunity? give example
a unique immune status which prevent effective virus infection into the host
sterilising immunity for influenza infection can be created by a vaccine that maintains high levels of neutralising serum antibodies
how does the incubation period of a pathogen effect immune response
short incubation doesn’t give time for memory cell activation
long incubation gives sufficient time so memory b cells can produce serum antibodies to clear the virus
what are the 7(9) types of vaccines
live attenuated virus inactivated or killed virus subunit: toxoid and bacterial capsular polysaccharide conjugate multitalented subunit nucleic acid: plasmid DNA and mRNA therapeutic
what is the target for the newly developed breast cancer vaccine
Mammaglobin-A secretory protein
how is the mammaglobinA breast cancer vaccine administered, why?
delivered by electroporation injection into muscle (accompanied by a small electrical charge to help delivery - opens muscle channels so muscle cells express protein)
why are cancer vaccines hard to develop
cancer originates from self, need to avoid problems tolerance
what are therapeutic vaccines
vaccines to treat already established vaccines
give some examples of live attenuated vaccines
oral polio
mmr
tuberculosis (BCG-bacilli calmette guerin)
vaccina (cowpox)
how is attenuation achieved
natural
serial passage and selection of mutants with reduced virulence or toxicity (repeated subculture by growing in bulk and growing sample from it)
chemical mutagenesis
what are the advantages of live attenuated vaccines
can replicate in host similar to pathogenic bro
larger more sustained dose of antigen
results in increased immunogenicity and more efficient production of highly efficient memory cells
gives long lasting and cell mediated immunity
fewer and lower doses required
what are the disadvantages of live attenuated vaccines
requires cold storage
may develop symptoms of natural disease
can’t be used in immune deficient people (causes serious complications)
reversion to virulent form possible
what are the two polio vaccines developed in 1950s/60s
Salk developed inactivated poliovirus vaccine
Sabin developed a live attenuated oral vaccine
what was the major issue with sabins polio vaccine
it was made from live attenuated virus that random mutagenesis caused reversion to virulent form causing the paralytic disease paralytic poliomyelitis
how were live attenuated vaccines made safer
recombinant dna technology - can now change large blocks of dna that’s harder to reverse
what genes are deleted in the attenuated malaria vaccine
p52 and p36
give five features of the sabin polio vaccine
works be colonising the intestine with three attenuated serotypes of polio virus (so they outcompete each other in gut)
requires three doses
only diff to virulent strain by 9 nucleotides
induces IgA IgM and IgG response
how are inactivated/killed vaccines made
by using either chemical reagents (formaldyhyde, glutaraldehyde) or heat to destroy the nucleic acid inside the pathogen so it can no longer replicate
give examples or inactivated or killed vaccines
Pertussis (whooping cough), cholera, typhoid fever, inactivated polio vaccines (Salk), influenza and zika.
what is critically important when inactivating a virus for vaccination
Critically important to maintain structure of key epitopes on surface antigens
what are the advantages of inactivated or killed vaccines
- Inactivated vaccines tend to be safer than live vaccines - can’t revert to virulent form.
- More stable and don’t require refrigeration – easier storage and transportation.
- Some may be freeze-dried.
- Commonly used against both viral and bacterial diseases.
what are the disadvantages of inactivated or killed vaccines
- Failure to inactivate pathogen (quality control important)
- Exposure of virulent pathogen to those making the vaccine.
- Need to be administered by injection.
- Produce a weaker immune response than live vaccines – generally requires boosters to illicit immune response.
- Generally only induce humoral immunity and NOT cell-mediated responses as organisms don’t replicate in host. (no good t cell response)
what are subunit vaccines
a specific purified macromolecule from pathogen.
what vaccine can be given to immunodeficent individuals
subunit vaccines/polysaccharide vaccines
what are the three main strategies/ types of subunit vaccines
toxoids, isolated capsular polysaccharides and purified key recombinant protein antigens.
give examples of subunit vaccines
Hepatitis B, Streptococcus pneumonia, diphtheria and tetanus.
what is a toxoid vaccine
exotoxins produced by pathogens are purified and inactivate to eliminate toxicity while maintaining immunogenicity
what is the host response to exotoxins
anti toxoid antibodies bind to and neutralise effect of exotoxin
what pathogens can toxoid vaccines be used for
diptheria and tetanus
what are bacterial capsular polysaccharide vaccines
type of subunit vaccine that involves a polysaccharide capsule coated in antibodies and/or complement increasing the ability of macrophages and neurophils to phagocytose
what two current vaccines use capsular polysaccharide vaccines
Current vaccine for Streptococcus pneumoniae consists of 13 antigenically distinct polysaccharides.
Neisseria meningitidis vaccine, cause of bacterial meningitis, consists of purified capsular polysaccharides
what are the advantages of subunit vaccines
- They are relatively easy to produce and are stable.
- Generally safer and better tolerated than whole organism vaccines.
- Can be given safely to immuno-suppressed people.
what are the disadvantages of subunit vaccines
- Generally requires strong adjuvants which can often induce a tissue reaction.
- Duration of immunity is generally shorter than live vaccines.
- They often need to be linked to carriers to enhance immunogenicity.
- Several doses must be given for proper life-long immunity.
- Induce little cell-mediated immunity
what are adjuvants, how do they act to this function?
: any material that can increase the humoral and cellular immune response against an antigen. - stimulate the innate immune system directly by acting on dendritic cells, macrophages, and neutrophils (improve antigen presentation) – leads to activation of adaptive immune system
what is the depot effect induced by adjuvants
at site of injection, adjuvants act by slowing the antigen release contain within the vaccine, prolonging the time they’re presented to the body (because they are oily)
what 4 mechanisms are used by adjuvants to augment and modulate immunogenicity
depot effect
attraction and stimulation of antigen-presenting cells
inflammasome activation
improve the delivery of the antigen
how do adjuvants cause attraction and stimulation of APCs
can cause local tissue damage to draw in APC stimulating them via pattern recognition receptors on the apcs.
describe the inflammasome activation caused by adjuvants
a multicomplex protein that forms intracellular complex, detects pathogenic organisms and causes inflammation, release of cytokines to surrounding area recruiting other innate cells. Responsible for redness on arm.
how do adjuvants improve the delivery of the antigen
improve delivery to the regional lymph nodes and the presentation of the antigen by improving uptake to apcs.
what are the advantageous characteristics of adjuvants
makes vaccines more cost effective (fewer doses needed)
effective innate immune signals including danger signals
goof immunomodulatory capacity
high specific antibody production
antigen specific clonal expansion
generation of cytotoxic t cells
long lasting adaptive immune response
makes antigen more potent (less dose required
)
what are the side effects of adjuvants
local reactions: redness, swelling, pain at injection site
systemic reactions: fever, chills, body aches
give 4 examples of adjuvants and what vaccines they accompany
aluminium based mineral salts - for anthrax and hep A
MF59 - for influenza
Monophophoryl lipid A - for hep B
virosomes - for hep A and influenza
what are conjugate vaccines
fusion of a highly immunogenic protein to a weak vaccine
what vaccine uses a conjugate
Haemophilus influenza type b (Hib) vaccine for Hib disease, tetanus, diphtheria, whooping cough, and polio
what major part of the immune repsonse do conjugate vaccines not induce
does NOT induce memory T cells specific for pathogen
what are multivalent subunit vaccines
incorporation of antigens into lipid vesicles (intracellular delivery) - designed to increase uptake and presentation of the antigens
give an example of a multivalents subunit vaccine, and describe its benefits
Immunostimulating complexes (ISCOM); antigenic proteins contained inside phospholipid monolayer.- good at fusing with cell surface of APC so good at delivery for loading onto MHC molecules to induce adaptive immune system response
why were recombinant viral vector vaccines developed?
Developed to overcome the reversion but retain the sustained antigen exposure
how are recombinant viral vector vaccines formed
take virulent pathogen, isolate antigen gene/s, get rid of all the other genes (no way of reversion). Then insert gene encoding antigen into an expression vector and put inside a different virus (completely nonvirulent) this construct is injected into the muscle and delivers dna encoding the antigen into the host cell.
what bacterial and viral diseases now used recombinant viral vectors
hiv, rabies, measles, covid
give examples of viruses that are used as vectors in recombinant vaccines
modified vaccinia virus Ankara (MVA), adenovirus (Ad) & adeno-associated virus (AAV).
how are recombinant viral vector vaccines administered
• Administered simply by scratching the skin causing a localised infection.
what plasmid gene is commonly used in recombinant viral vector vaccines - and how do you test the success of antigen gene insertion?
Thymidine Kinase gene.
To test, add thymidine analogue called BrDU.- in cells with intact TK gene (unsuccessful implant) thymidine kinase converts nucleotide into nucleoside which is then incorporated into the viral genome. – this kills all the viral particles
how does the Astrazeneca/Oxford Uni ChAdOx1 nCoV-19 vaccine work
Adenovirus vector-based, (tough coat, no cold storage)
Encodes codon optimised full length spike protein into modified chimp adenovirus. Deliver antigen coding gene into cells but cannot replicate.
Host cell machinery produces spike protein, some expressed on cells surface other loaded onto mhc molecule and put on the surface
Helps activate helper t and cd8 t cells. Give good humoral (neutralising antibodies) and cell mediated (cytotoxic t-cell activation) response
what are nucleic acid vaccines
vaccines that involves the administration of genetic material encoding the desired antigen. in the form of either plasmid containing DNA or a lipid encapsulating mRNA so the encoded antigen is made and expressed by the host cell itself
why are most DNA vaccines administered via intramusclular injection
- muscle avidly takes up DNA.
- relatively low turnover rate of muscle cells prevents dispersion in dividing cells – prolonged exposure
give examples of DNA vaccines
Hepatitis B, malaria, HIV, Influenza, Zika, Dengue fever, HPV, cancer, and Coronavirus.
what are the two main routes of DNA vaccines
Direct: DNA taken up directly by antigen presenting cells at point of injection, these express antigen and load onto MHC molecules to display on surface
Indirect: DNA taken up by non APCs (keratinocytes and myocytes), express antigen or released ectracellularly. at some point transfer to APCs where expressed on MHCs on surface
what are the advantages of DNA vaccines
- Low intrinsic immunogenicity of nucleic acids
- Induction of long-term immune responses
- Induction of both humoral and cellular immune responses
- Possibility of constructing multiple epitope plasmids
- Heat stability
- Ease of large-scale production
what are the disadvantages of DNA vaccines
- Effects of long-term expression unknown
- Formation of antinucleic acid antibodies possible
- Possible integration of the vaccine DNA into the host genome
- Concept restricted to peptide and protein antigens
- Poor delivery
- Poorly immunogenic in man
what are the basic structural elements of mRNA vaccines
- 5’ cap: helps achieve superior translational performance by stabilizing the mRNA molecule and directing the immune response.
- 5’ and 3’ untranslated region (UTR): contain various regulatory sequences associated with the stability of mRNA, recognition of mRNA by ribosomes, interaction with the components in translational Machinery.
- Coding region
- Poly(A) tail: maximises the translational performance of mRNA vaccines.
what are the advantages of mRNA vaccines vs DNA vaccines
- mRNA vaccines appear to perform better.
- Does not need to enter nucleus.
- Safer – no possibility of integration into host genome.
what are the disadvantages of mRNA vaccines
• Stability – requires storage at -80 °C or -20°C
what are antiidiotypic vaccines
A vaccine made of antibodies that see other antibodies as the antigen and bind to it. Can stimulate the body to produce antibodies against tumor cells.
comprise antibodies that have three-dimensional immunogenic regions, designated idiotopes, that consist of protein sequences that bind to cell receptors. Idiotopes are aggregated into idiotypes specific of their target antigen. An example of anti-idiotype antibody is Racotumomab.
mainly used for high risk cancer patients
