L25: Immunisation and vaccine Flashcards
Immunisation and ideals (7)
Deliberate induction of an immune response:
- Single administration gives lifetime immunity
- Needleless delivery
- Stable at ambient temperature
- Cheap and simple to manufacture
- Zero side effects
- Simple surrogate marker for effective immunisation
- Works therapeutically if already infected
Active immunisation (4)
- Delivery of antigen
- Induce specific effector functions
- Induce imunological memory
- Boosted by re-exposure to antigen or pathogen encounter
Passive immunisation (4)
- Transfer of antibodies, antisera, or T cells of desired specificity
- Lasts as long as the transferred material
- No memory
- Boosting of T cells by combined active/passive immunisation
Vaccine
Aim to induce a desired immune response, three key components:
1. Antigen (protein, carbohydrate or lipid)
2. Delivery system (virus, gene gun, needle and syringe)
3. Adjuvant to enhance immunity to antigen by stimulating innate immune response
Majority of vaccines work by inducing neutralising antibodies against the antigen.
Vaccine antigens - requirements and choice
Need proteins and peptides for T cell responses (memory and efficacy) and stable arrays of epitopes for B cell responses. Choices:
1. Organism - live attenuated, related, killed
2. Subunit/particle - multimeric or monomeric
3. Proteins - structural/nonstructural, receptor
4. Peptides - defined epitope or random
5. DNA - encoding relevant proteins
6. Carbohydrate
7. Lipid
Formulation allows easy degradation or stability
Live attenuated vaccines (4)
- pathogenic virus is isolated from patient and grown in human cultured cells
- Cultured virus is used to infect monkey cells
- Virus acquires many mutations that allow it to grow well in monkey cells
- Virus no longer grows well in human cells (it is attenuated) and can be used as a vaccine
Delivery of a vaccine antigen (4)
- Controlled delivery of antigen to the MHC Class 1/MHC class 2 pathway in professional APC
- Elicit the correct type of immune response
- Induce (long lasting) memory
- Avoid immunological toelrance/overcome mucosal tolerance
Adjuvant
Any substance that enhances the immunogenicity of an antigen mixed in with it. Convert soluble antigen into particulate form for uptake and slow release (adsorption of antigen on alum, emulsification in mineral oils, colloid particles of immune stimulatory complexes ISCOMS). Induction of local inflammation enhancing APC attraction and maturation
Delivery systems (6)
- Protein/adjuvant mixtures
- Particles
- Live vectors (adenoviruses, poxviruses)
- DCs - pulsed/loaded with peptide or apoptotic cells
- Gene gun - choice of target sites
- co-delivery of activating cytokines
Assessing vaccine efficacy (5)
- Preclinical: efficacy in an animal model
- Clinical Phase 1: safety, immunogenicity, dose range
- Clinical Phase 2: safety, immunogenicity, protection against infection in a defined at-risk population
- Clinical Phase 3: safety, protection against disease all-comers, surrogate marker for protection
- Post marketing surveillance: antibody (critical and standardised, virus neutralisation by serum)
Reasons for vaccination
- Protects community and individual
- Herd immunity: immune individuals reduce number of susceptible hosts; protects unimmunised, young and those who are immunisation ineffective
- Vaccine safety: generic - killed and live vaccines; specific - immune enhancement
Questions when developing a new vaccine (4)
- Is natural immunity following infection protection
- What’s the natural history and epidemiology of the infection (target population and how infection causes disease)
- How can you prepare antigen (live, killed, recombinant)
- Is the targeted antigen “stable”: antigen drift and shift, immune selection pressure
