Week 4 Flashcards
Objectives of Immunization Programs
- Prevent, control, eliminate, eradicate vaccine preventable diseases
- By directly protecting vaccine recipients and indirectly protecting vulnerable peoples
Vaccination Definition
Intentional exposure to pathogens in a form that cannot cause infectious disease
Vaccine Purpose
Recipient to develop long-term immune protection against pathogen
Benjamin Jesty
- Inoculated family with pus from cowpox blister of a cow
- Protect from smallpox
- Fear of wife & children becoming victims of smallpox
- Never published results
Edward Jenner
- Demonstrated immunity to smallpox
- Inoculating 8 year old body with cowpox virus
- Boy did not acquire disease
Smallpox Vaccine Significance
- First & only procedure that has fully eliminated & eradicated the disease as of 1980
- Vaccine no longer needed
Louis Pasteur
- Created vaccines against chicken cholera, anthrax, rabis
- Isolate, inactivate using heat & inject
- First to propose germ theory of disease
Tetanus
- Leads to general rigidity and convulsive spasms
- Death rate 10% of cases
Measles
- Causes bronchopneumonia - 1 in 10 cases
- Encephalitis (15% fatal) - 1 in 1000 cases
Rubella
- Mild disease
- Encephalitis - 1 in 6000 cases
- Congenital rubella syndrome - during pregnancy
Cost
- Savings in health costs
- Immunization program cost less than treating disease
Andrew Wakefield
- Claimed MMR vaccine causes autism in 1998
- Vaccination rates dropped
- Retracted Feb 2000 - no link between MMR & autism
- One of the most serious fraud in medical history
Herd Immunity
- Protects susceptible individuals by stopping transmission
- Risk of infection reduced when # of individuals who can spread pathogen is reduced
Sustained Transmission
- Transmitting case
- Susceptible
- Transmitting case
- Susceptible
Transmission Terminated
- Transmitting case
- Immune
- Susceptible indirectly protected
Herd Immunity Effectiveness
- Sufficient # of people must be immune
- Depends on transmissibility of infectious agent
Vaccine Efficacy
Ability of vaccine to prevent illness in vaccinated people within a controlled study
Vaccine Effectiveness
Vaccine’s ability to prevent illness in the real world
Reproduction Number R0
- Average # of transmissions expected of a single case when introduced into susceptible population
- Highly infectious = high R0 rate (measles)
Disease Outbreaks
Can occur when immunity falls below a critical % in a population
Vaccine Hesitancy
Delay in acceptance/refusal of vaccination despite availability of vaccine services
Vaccine Exemptions
- Medical - previously infected, condition preventing vaccine
- Non-medical - philosophical, religious
Vaccines with High Hesitancy
- MMR
- HPV
- Covid-19
Calculation
- Individuals engagement in extensive information searching
- Time & ability to search for information to make decision
Collective Responsibility
- Willingness to protect other by one’s own vaccination
- Community (herd) immunity
Confidence
- Trust in effectiveness/safety of vaccines
- Reliability & competences of healthcare services
- Motivation of policy makers who decide on vaccines
Convenience
- Physical availability
- Ability to comprehend vaccine information/health literacy
- Appeal of immunization services to effect uptake
Complacency
- Perceived risk of vaccine preventable diseases is low
- Vaccination not deemed necessary to prevent disease
Immunizing Agents
- Active or passive
- Depending on process which they confer immunity
Passive Immunization
- Transfer of preformed antibodies from one person to another
- Provide immediate temporary infection
- Reducing severity of illness caused by infectious agent
- Transferred antibodies degrade overtime
Passive Immunization Purpose
- Transplacental transfer up to 1 year
- Provide protection when active vaccine not available
- Rapid protection required post exposure
Acute Immunization
- Stimulation of immune system to produce specific antibodies - immunologic memory
- Lasts for many years or lifetime
- Survive infection of disease causing form of organism
- Vaccination can also create immunologic memory
Active Immunity
- Natural infection
- Artificial vaccination
Passive Immunity
- Natural maternal antibodies
- Artificial monoclonal antibodies
How Vaccines Work
- Biological product designed to induced safe immune response
- Weakened/killed form of disease injected into body
- Body creates antibodies to fight the germs
- If the actual disease germs ever attack the body the antibodies destroy them
Ideal Vaccine
- Safe - low risk of adverse effects
- Effective in providing lifelong protection
- Inexpensive
- Stable during shipping & storage
- Easy to administer
Inactivated Vaccines - Whole
- Cannot cause disease meant to prevent due to virus being dead
- Bacteria modified to remove pathogenic response
- Immune response less than live vaccines
- Multiple doses
- Primary vaccination - prime immune system
- Booster doses may be required to boost antibody levels
Subunit Inactivated Vaccines
- Toxoid
- Polysaccharide-based (pure, conjugate)
- Use specific pieces of germ
Live Attenuated Vaccines
- Attenuated (weakened) form of wild virus/bacterium
- Must replicate/grow within person to produce immune response
- Immune response identical to natural infection
- Produce immunity with 1 dose (excludes oral admin)
- 2nd dose ensures almost all recipients protected
- Severe reactions possible - contraindicated in immune compromised individuals
- Fragile store carefully
Under Attenuated
- Cause disease
- Bacteria not weakened enough
Over Attenuated
Does not provoke enough immune response
Inactivated Vaccine Microbes
- Cannot be attenuated
- Have oncogenic potential
Polysaccharide Vaccines
- Inactive
- Sugar molecule chains
- T cell independent response
- Stimulate B cells without T helper cells
- Young children don’t respond consistently due to immune system immaturity
- Repeat doses do not cause booster response - IgM mainly produced
Conjugation
- Polysaccharide combined with protein molecule
- Changes immune response to T cell dependent
- Antibody booster response to multiple doses
Pure Polysaccharide Examples
- Pneumococcal
- Meningococcal
- Salmonella typhi (Vi)
Conjugate Polysaccharide Examples
- Haemophilus influenzae type b (Hib)
- Pneumococcal
- Meningococcal
Toxoid Vaccines
- Use toxin (harmful product) made by germ
- Create immunity to parts of germ that cause disease not whole germ
- Protein based toxin is harmless & used as antigen in vaccine to create immunity
- Toxin converted to toxoid with heat/chemicals
- Toxin absorbed by aluminium/chemical salts
- Antigens remain intact
- Cannot cause disease they prevent
- Vaccine antigens not actively multiplying
- Stable - no response to temp, light
- Require several doses
- Need adjuvants - not highly immunogenic on own
mRNA Vaccines in Canada
Pfizer & moderna COVID-19 vaccines
Katalin Kariko
- Hungarian biochemist
- PHD in biology
- Denied funding in mRNA many times
- Senior VP develop Pfizer
How mRNA Works
- Change instructions of body to build a defense against virus
- Technology creates mRNA sequence that body recognizes as if its own cells
- Lipid nanoparticle system to deliver mRNA to dendritic cell
- Stays in cytoplasm
- Ribosomes read instructions & manufacture protein
- Dendritic cells place proteins on surface
- Travels to nearby lymph node to present surface protein to other cells of immune system
- Helper T cells communicate with B cells to develop antibodies that fit onto protein
- B cells then produce antibodies to identify & neutralize
- Survives 1-3 days
- Cellular enzymes breakdown RNA once used
mRNA Structure
- Single strand molecule
- No thiamine
mRNA Vaccine Advantages
- Easier & safer to produce than vaccines that require weak/inactive pathogen
- Easily altered for protein spikes/common viral mutations
mRNA Vaccine Disadvantages
- Challenge to deliver to cells as innate immune system can destroy (use lipid nanoparticles to protect mRNA)
- Lipid nanoparticles require uninterrupted freezing/refrigeration - easily damaged (stick protocols for transport & delivery)
Future of mRNA Vaccines
- Likely many more to come
- Further work on stabilization methods to ease transport & admin
- Limitless possibilities for protection against pathogens
- Personalized vaccine to targeting genetic mutations in cancer cells