Lecture 8: Vaccines Flashcards
What is immunization?
Process by which an individual’s immune system becomes fortified against an immunogen
What are the 2 types of immunization?
- Passive: transient
- Active: long term
How is passive immunization accomplished?
- Maternal antibodies
- Monoclonal antibodies and antitoxins
What is vaccination?
Practice of artificially inducing immunity
What is the goal of vaccination?
Immunological memory - to stimulate both arms of the adaptive immune system (humoral and cell-mediated)
What should a vaccine have?
The maximum effect at a minimal danger
What are the 5 types of vaccines discussed in class?
- Inactivated or “killed”
- Live, attenuated
- Subunit and conjugate
- Recombinant vector
- DNA
How are inactivated or “killed” vaccines made?
By heating or chemically treating the pathogen, however they must maintain the physical structure.
What are the pros and cons for an inactivated or “killed” vaccine?
Pro
- Non-infectious
- Stabile
- Good shelf life
- Easy to transport
- Assurances of completely killed
Con
- Less effective at activating cell-mediated response
- Requires boosters
Ex. Influenza, plague, cholera, Hep A, rabies
What are adjuvants?
Substances incorporated along with antigen in a vaccine.
What is the role of adjuvants?
They decrease the amount of antigen necessary to induce an immune response.
- Prolong antigen persistence
- Enhance costimulatory signals
- Increase local inflammation
- Stimulate lymphocyte proliferation
- Enhance size of antigen for phagocytosis
How are live, attenuated vaccines made?
The pathogen is weakened due to prolonged growth in abnormal conditions. Conditions can include different temperature, pH, host. They can also be genetically engineered.
What are the pros and cons for a live, attenuated vaccine?
Pros
- Strong immune response
- Activates both arms of the adaptive immune response
Cons
- Possibility of reversion
- Complications of over-response
- Cannot use in immunocompromised
- Storage concerns
How are subunit vaccines made?
They are specific, purifies macromolecules such as inactivated exotoxins that produce toxoids. Can also include polusaccharides and glycoproteins
What are the pros and cons for subunit vaccines?
Pros
- Stimulate humoral response
- Minimal danger of infection
- Stable/good shelf life
- Portable
Cons
- Usually requires a booster
- Does not stimulate cell-mediated immunity
How are conjugate vaccines made?
A subunit from a target pathogen is irreversibly bound in a ‘conjugate’ with bacterial proteins. The B-cell will engulf and present epitopes from the vaccine. The conjugate elicits an enhances immune response.
What are the pros and cons for conjugate vaccines?
Pros
- Stimulates both humoral and cell-mediated
Cons
- More complex
How is a recombinant vector vaccine made?
Exogenous genes from the pathogen are inserted into a non-virulent virus or bacterium
What are the pros and cons for conjugate vaccines?
Pros
- Stimulated both humoral and cell-mediated response
- No real danger of infection
Con
- Pre-existing immunity to carrier might block effect (must use different carrier for booster)
How are DNA vaccines made?
Pathogen plasmid DNA with gold particle injected into the muscle through a gene gun. Cells will take up the DNA, incorporate it and begin o form proteins of antigens.
What are the pros and cons for DNA vaccines?
Pros
- Both cell-mediated and humoral immunity
- Prolonged antigen expression renders significant immunological memory
- Easier storage that live attenuated
Cons
- Still experimental
- Deliver is non-trivial
How are vaccines tested? 3 different ways
- Laboratory testing (vaccine dev. & cell culture)
- Animal model (animals must be susceptible to pathogen and show same symptoms as humans)
- Clinical trials in humans
Explain the components of a Phase I clinical trial.
- Small number of participants (20-100)
- Determine vaccine dosage
- Evaluate for side effects
- FDA must approve vaccine as an Investigational New Drug (IND)
Explain the components of a Phase II clinical trial.
- Larger number of volunteers (>200)
- last few months - years
- Controlled study (control vs. placebo (or existing vaccine))
- End Points: Safety & Effectiveness
Explain the components of a Phase II clinical trial.
- Large number of volunteers (100s - 1000s)
- RCT (control vs. placebo (or existing vaccine))
- How you get efficafcy
How is efficacy measured?
Efficacy = [(ARU-ARV)/ARV] * 100
What is effectiveness?
It is the “real world” performance.
Important to note 1-2 of every 20 people immunized will not have an adequate immune response
What is herd immunity?
Because vaccinated people have antibodies against a pathogen, they will protect those who are unvaccinated. (75-95% of coverage is needed)
Who decides vaccine recommendations?
HD and expert physician organizations
- When should vaccines be used
- Who should receive it
- Weight the risks and benefits of the vaccine and costs of vaccination
What is the legislation regarding vaccination?
States decide which vaccines are required by law, but all 50 states have school immunization laws. Can be exempted due to... - Medical reasons - Religious reason - Philosophical reasons
What are the challenges for vaccine development in the developed world?
- Cost (Need facilities, regulation, litigation)
- Market Size (Usually purchased once, >50% bough by public sector)
What are the challenges for vaccine development in the developing world?
- Transportation (must be heat stable/UV protected)
- Cost (single dose effective)
- Update in mucosal membranes
- Syringe use
- Trained health workers
How to address the issue with heat/freeze/UV with vaccines?
- Temperature-sensitive and UV sensitive labels
- Lower-cost solar refrigerators
- Phage-change material used in vaccine carriers prevent the freezing of vaccines
- Thermo-stable vaccines
How to address the issue with syringe use/healthcare workers with vaccines?
- Use one-time use or disposable syringes
- Need for a needle-free delivery (jet injectors)
- Intradermal adapter (standardized injection depth/angle, less human error)
What is antigenic drift?
The gradual, spontaneous, minor change. Can include point mutations.
What is antigenic shift?
A sudden and unique change. Can be cause by reassortment.
