L29 - Challenges To Vaccine Design Flashcards
What are the pre-1980s vaccines
Attenuated, killed, toxoid and antigenic subunits
What are the post-1980s
- virus-like particles
- outer membrane vesicle
- protein-polysaccharide conjugate
- viral vectored
- nucleic acid vaccine
What is virus like particles
Self assemble to loose like virus bc has capsid. Used for delivery for vaccine and drug molecule. Won’t replicate bc no DNA
Outer membrane vesicle
Gram -ve forms vesicles that secretes enzymes and communicate w each other
- low scale production
- increases yield and inactivates LPS
Protein polysaccharide conjugates
Polysaccharides alone (like those on bacterial surfaces) can’t be presented to T cells, so they trigger weak B cell responses. By conjugating the sugar to a protein, B cells can bind the sugar, internalize the whole complex, and present the protein portion on MHC II to T helper cells. This allows T cell help, leading to affinity maturation, class switching, and stronger, long-lasting immunity.
How does the Oxford-AstraZeneca (ChAdOx1) COVID-19 vaccine work?
The vaccine uses a chimpanzee adenovirus vector (ChAdOx1) to deliver DNA encoding the SARS-CoV-2 spike protein
Administered via intramuscular injection, it activates dendritic cells (DCs) which process the antigen and present it to T cells, while soluble antigen also activates B cells. This leads to a strong, S protein-specific immune response, generating helper T cells, cytotoxic T cells, memory cells, and long-term immunity.
How does the Pfizer and moderna COVID-19 vaccine work?
Targets spike proteins
- mRNA enclosed in lipid nanoparticles. Full length S protein with 2 proline substitutions
What are the vaccine delivery routes
Intranasal, aerolised, oral, intramuscular,m intraperitoneal, intradermal, intravenous, in ovo
What is flumist
Live attenuated flu virus strains sprayed into nose.
What are vaccine adjuvants?
A vaccine adjuvant is a substance added to vaccines to enhance the immune response to an antigen
How do adjuvants activate dendritic cells
Mimicking components of microbes that bind to PRR on APC
What are critical criteria’s of adjuvant
• Extend the presence of antigen (reservoir)
• Locally activate macrophages and lymphocytes
• Support the local production of cytokines
• Activate antigen presenting cells, support absorption, migration and present antigen
Benefits and risks of vaccine adjuvants
Benefits:
• Enhance / accelerate the
• Increase reactogenicity immune response
• Prolong the immune response
• Focus the immune response
• Diversify the immune response
activation
- Immune mediated disease
• Increase antibody affinity
- Organ specific
• Improve long term memory
Risks
Systemic effects, e.g., inflammation, fever, myalgia
- Inflammatory diseases
• Special Patient Populations
Why in some cases live attenuated vaccines are not good
Can lead to revertant mutants that does not help clearing but spreads the pathogens
Risks and advantages of live attenuated vaccines
Advantages:
• Activates all phases of the immune system
• Provides more durable immunity; boosters are required less frequently
• Low cost
• Quick immunity
Disadvantages
• Secondary mutation can cause a reversion to virulence
• Can cause severe complications in immune-compromised patients
• Some can be difficult to transport due to requirement to maintain conditions (e.g. temperature)
Hypocretin specific T cells found in patients suffering narcolepsy. How?
Brain neuropeptide resembles neural protein and immune vaccine is recognising hypocretin.
Antigenic drift in vaccines
Vaccines change every year due to anti8gen variability
What are the steps in vaccine development
- recognise disease
- identify etiologic agent
- grow agent
- establish animal model
- identify immunologic correlate
- inactivate or attenuate agent
- protocol
- get approval
- trials
How can we measure vaccine effectiveness using radioimmunoassay?
Radioimmunoassay (RIA) detects and quantifies antibodies in blood after vaccination. It works by:
• Using radioactively labeled antigens that bind to specific antibodies in a sample.
• The amount of radioactivity measured reflects the amount of antibody produced.
This helps determine whether the vaccine successfully triggered an immune response—more antibodies = more effective vaccine. RIA is sensitive and precise, but modern methods like ELISA are now more common.
