Vaccines Flashcards
(19 cards)
What is herd immunity? What the threshold specific for?
Maintenance of a critical level of immunity:
Population-scale immunity.
Not everyone must be immune to protect a population
Virus spread drops when the probability of infection falls below a critical threshold.
Specific for virus and population
What is the differences between active and passive vaccines? Examples?
Active:
- Modified form of the pathogen or material derived from it
- Long term protection
- Attenuated, inactivated, fractionated, recombinant, etc. vaccine
Passive:
- Receive products of the immune response ((m)Abs or immune cells)
- Short term protection
- Tetanus (stivkrampe), or Hepatitis A vaccines
Describe the two types of passive immunity
Articficial:
Infusion of serum or plasma containing high concentrations of Abs/immune cells
Natural:
- Transfer of Abs by the maternal circulation in utero through the placenta
- Transfer of Abs via breast milk
What are the requirements of an effective vaccine?
- Induction of an appropriate immune response
(want Th1 that favors killing of intracellular
pathogens, not Th2 that favors Ab production)
- Do we need mAb or T cell response? - Vaccinated individual must be protected
against disease caused by a virulent form -
producing a response is not enough - Safety: no disease, minimal side effects
- Induce protective immunity in the population
- Long-lasting effects
- Low cost, genetic stability, storage
considerations, delivery (oral vs. needle)
What types of vaccines exist?
- Non-recombinant:
- Attenuation
- Inactivated
- Fractionated (subunit)
- Recombinant:
- Virus vector
- DNA/mRNA
- Protein: virus-like particle or subunit
What is the principles of inactivated vaccines?
Infectivity is eliminated (cannot replicate).
Antigenicity is not compromized.
Can use chemical procedures (formalin, beta-propriolacetone, nonionic detergents…)
Give a brief explanation about the inactivated influenza vaccine. Principles and challenges
- Virus grown in embryonated chicken eggs,
formalin-inactivated or detergent or
chemically disrupted virions.
Vaccines produced in cell culture - 60% effective in healthy children and adults
<65 yrs. - Serum Abs to spike proteins: HA (hemagglutinin) and HA (neuraminidase)
- Problematic: high mutation rate → change
each year, must select new strains
- Problematic: high mutation rate → change
What is a typical process when selecting an influenza virus vaccine?
- Surveillance (entire period)
- Select strains (jan-feb)
- Prepare reassortants (jan-mar)
- Standardize Ag (jan-may)
- Assign potency (mar-aug)
- Review/licence (may/june)
- Formulate/test/package (may-aug)
- Vaccinate (sept-dec)
What is the differences between antigenic drift and antigenic shift? Example: Influenza virus
Drift:
Accumulation of several minor genetic mutations
Shift:
Mixing of genes between IVs from different species
What are the principles for subunit vaccines? What are advantages and disadvantages?
Break virus into compartments, immunize with purified components.
Can be done using recombination:
Clone viral gene, express in bacteria, yeast, insect cells, cell culture, purify protein.
Ag usually capsid or membrane protein.
Advantages:
- Recombinant DNA technology is fast
- No viral genomes/infectious virus
Disadvantages:
- Expensive
- Injected
- Poor antigenicity: don’t cause infection and
give poor activation of adaptive responses
- Require adjuvants to mimic inflammatory
effects
What are adjuvants?
- Act to accelerate, prolong, enhance or
shape the specific immune response against antigens/viruses/pathogens. - Compounds added to stimulate early
processes in immune recognition. - Produce more robust acquired immune
response.- Slow release of Ag at site of inoculation ->
higher concentration - Inflammation
- Slow release of Ag at site of inoculation ->
Describe the approach for developing an universal influenza vaccine. Why is it difficult to achieve?
Aim: protect against Ag drift variants
- Based on HA protein
- Use synthetic peptide from the conserved
stalk region (memb. proximal) of HA- Mediates membrane fusion. Conserved.
Can offer cross-protection.
- Mediates membrane fusion. Conserved.
- HA globular head (memb. distal) mediates
receptor binding. Highly variable between
strains.
Problem: HA head region is variable.
- Most Ab directed against head
- Stem = immuno-subdominant
Solution: Redirect Ab response to stalk
- Exchange head domains in vaccine -> memory
generated against stem.
What are the principles of attenuated vaccines?
- (Reduced) viral replication occurs -> stimulates
immune response. - Infection -> mild/inapparent disease
- Often requires several doses -> self-amplifying
Made empirical or by recombinant DNA tech.
- Empirical grown in other species: isolate virus from patient, grown in human culture cells, infection of e.g., monkey cells, mutations acquired, virus no longer grows well in human cells.
Modern:
- Make 3’ UTR deletions (alter viral gene
expression regulation
- Remove virulence proteins
- Insert gene from virus A into an attenuated
strain of virus B.
What are the principles of mRNA vaccines? How are mRNAs designed? Advantages/disadvantages? Example: COVID-19
- Rapid development; need only sequence of
virus. - Injected into body, usually within lipid
nanoparticles (LNPs) - LNPs fuse with cells.
- RNA seq is translated by ribosomes to make
protein (parts). - No infectious virus
Design:
- Optimization of translation and stability
- Modulation of immunogenicity
- Reduce innate stimulation to avoid translation
block.
- Innate immune sensing
- Delivery
- Elements to enhance translation: 5’ cap and 3’
ribosome binding (efficiacy), kozak seq
(translation initiation seq)
Advantages:
Safe, rapid, flexible to mutations.
Pfizer/BioNTech + Moderna: no need for adjuvants - LNPs (and mRNA) are immunogenic
Disadvantages:
Unstable -> need to be kept frozen
What is often the target of SARS-CoV-2 vaccines?
Pre-fusion form of spike protein.
- mRNA vaccines based on stabilized mRNA encoding prefusion SARS-CoV-2S
- Janssen -Ad26 vector-based encoding prefusion-stabilized SARS-CoV-2 spike immunogen.
- Novax Nuvaxovid composed of dull-length spike protein that is stabilized in its prefusion conformation
What are lipid nanoparticles and why are they used in vaccines?
- Spherical vesicles made of ionizable lipids.
- Positively charged at low pH eenabling RNA
complexation - Neutral at physiological pH -> reduced toxic
effects. - Ionizability of lipidss at low pH (likely ) enables
endosomal escape
-> cargo into cytoplasm - Taken up by APCs at injection site
- APCs present S protein
- Usually contain helper lipids
Describe the subunit vaccine for human papillomavirus (HPV)
- Cancer vaccine
- > 200 genotypes: vaccines often target several
HPV = non-enveloped, L1 is major capsid protein
- Purified L1 protein forms virus-like particles
(VLPs).- Elicits virus-neutralizing Ab response
->
High imm
- Elicits virus-neutralizing Ab response
Describe the subunit vaccine for human papillomavirus (HPV)
- Cancer vaccine
- > 200 genotypes: vaccines often target several
HPV = non-enveloped, L1 is major capsid protein
- Purified L1 protein forms virus-like particles
(VLPs).- Elicits virus-neutralizing Ab response
->
High imm
- Elicits virus-neutralizing Ab response
Describe the subunit vaccine for human papillomavirus (HPV)
- Cancer vaccine
- > 200 genotypes: vaccines often target several
HPV = non-enveloped, L1 is major capsid protein
- Purified L1 protein forms virus-like particles
(VLPs).- Elicits virus-neutralizing Ab response
->
High imm
- Elicits virus-neutralizing Ab response
