Vaccination Flashcards
What are the different types of vaccines?
- Live attenuated viruses (measles, yellow fever): most immunogenic but do present safety concerns
- Inactivated viruses (polio, TBE)
- Polysaccharides (haemophilus infl.)
- Protein subunits, Inactivated split viruses (seasonal influenza)
- Virus-like particles (hep B, HPV)
6 (not licensed). DNA, Viral vectors, mRNA: gene-based vaccines may have stronger immune responses as they mimic viral infection
2, 3, 4 & 5 => need of adjuvants
How do DNA, viral-vectored and mRNA (gene-based) vaccines work?
With these vaccines, a gene encoding for an antigen is used: this generally mimics a viral infection
What can be said about DNA vaccines?
- Plasmid DNA encoding for an antigen is injected
- Needs help for delivery to the cell nucleus (electroporation)
• Good prime but often requires boost with different vaccine types for antibody responses
What can be said about Viral Vector vaccines?
- A replication-deficient modified virus (viral vector) carries the gene encoding for the antigen
- No need for delivery help but might require an adjuvant
- Vectors generate a response too
- Need for different vectors for boost/other vaccinations
What can be said about mRNA vaccines?
- RNA encoding for an antigen is injected
- No need to reach cell nucleus but requires formulation (in lipid nanoparticles or other)
• Very potent adaptive but also innate response, needs modifications to tune it down (the response is too strong, so there is side effects)
What do naïve B-cells differentiate into after antigen presented?
In the marginal zone:
- IgM memory B-cell
- short lived plasma cell
After the germinal center (T-cell co-activation):
- IgG memory B-cell
- Long lived plasma cell (in bone marrow)
- Memory T-cell (not from B-cell ^^’)
=> these 3 come after immunoglobulin affinity maturation
How does the immunoglobulin affinity maturation happen (somatic hypermutation)?
AID enzyme is expressed to insert mutations in hotspots in both V and C regions
While point mutations occur in V, DNA breaks occur in the C region
DNA is re-joined by DNA repair (non-homologous end-joining)
=> These mutations lead to a stronger affinity and will be selected for further maturation
What is Protective (antibody) thresholds or ”Correlates of protection” and what does it assess?
It is the minimum amount of antibody required for protection against a pathogen
It is used to assess whether a vaccine works
What is the difference between the heavy chain and the light chain in antibodies?
Heavy chains has V,D & J segments whereas light chain has only V and J segment
What is reverse vaccinology?
Isolating an naturally produced antibody => sequence it and synthesize one (germline antibody) => do a binding essays where the highest affinity germline antibody binds to an engineered protein complex similar to the virus => inject that protein complex as a vaccine
What is the difference of Covid-19 compare the SARS or MERS infectivity and lethality wise?
COVID-19: higher infectivity and lower lethality
What does the receptor binding domain of Covid-19 binds to?
Interacts with the angiotensin-converting enzyme 2 (ACE2) receptor
What are the 3 phases of clinical trials?
• Phase I: a small group of people receives the trial vaccine (selecting the best dose with the less side effects)
• Phase II: the clinical study is expanded and vaccine is given to people who have characteristics (such as age and physical health) similar to those for whom the new vaccine is intended
• Phase III: the vaccine is given to thousands of people and tested for efficacy and safety (longest phase)
• Many vaccines undergo Phase IV: ongoing studies after the vaccine is approved
and licensed
What is the difference between traditional and accelerated timelines of vaccine development?
Accelerated timelines overlap the clinical trials with FDA review and manufacturing => prevents undertaking safety risks but presents financial risks
Traditional timelines prevent undertaking safety or financial risks but it does take years to complete
What is the goal of a preventive vaccine?
It is to generate B-cell and antibody responses above the level required for protection to infection or re-infection (protective antibody threshold)
