9: Vaccination Flashcards
Vaccination
deliberate exposure to harmless antigenic material which stimulates immune system
Aim of vaccination
elicit T cell response inducing production of immunological memory to provide protection against disease if later encountered
- reducing morbidity and mortality of infectious disease targeted by vaccine
Type of immunity involved in vaccination
Artificial active immunity
Artificial active immunity is
artificial - haven’t encountered antigen naturally in wild form
active - generating own antibodies and own immune response against antigen
Acquired Immunity
immunity that develops during lifetime
Types and examples of active immunity
Natural - antibodies developed in response to infection
Artificial - antibodies developed in response to vaccination
Types and examples of passive immunity
Natural - antibodies received from mother, via breast milk
Artificial - antibodies received from a medicine/gamma globulin injection or infusion
Features of an ideal vaccine 7
completely safe
easy to administer
single-dose, needle-free
cheap
stable
active against all variants
life-long protection
Herd immunity
more immune individuals = less likely that a susceptible person will come into contact with someone who has the disease
How do vaccines work in community
Herd immunity
Reducing R0 number
R0
how many people an infected person is able to infect
aim of immunisation is to reduce R0 to less than 1
If R0<1
Infection will die out in long run
If R0>1
infection will be able to spread in population
What are vaccines composed of
Antigen - to stimulate immune response to target disease
Adjuvant (alum) - enhance and modulate immune response
Excipients = inactive substance serving as a vehicle or medium for vaccine;
buffer, salts, saccharides and proteins to maintain pH, osmolarity and stability of vaccine
Preservative e.g phenoxyethano
Water
5 types of vaccines and examples
Inactivated Protein e.g Tetanus toxoid
Recombinant protein e.g Hep B
Live Attenuated Pathogen e.g Polio/BCG
Dead Pathogen e.g Split Flu vaccine
Carbohydrate e.g S. pneumoniae
Inactivated protein vaccines
Example: Tetanus toxoid
Description: chemically inactivated form of toxin
Mechanism: induces antibody, antibody blocks toxin from binding in nerves
Pros of inactivated protein vaccines
simple to produce
cheap
relatively safe
highly immunogenic (stimulates immune response very well)
high protective efficacy
Cons of inactivated protein vaccines
Not all pathogens produce toxins
good understanding of toxin produced needed
sometimes toxin isn’t fully inactivate
Live attenuated vaccines
Example: MMR, Chickenpox, LAIV (flu), OPV (polio), BCG
Description: contain mutations which hinder ability to cause disease, but can be recognised by immune system as foreign (lose virulent factors)
Mechanism: “live” so can replicate inside host, recognised as foreign - generate innate response and boost immune response
Cons of live attenuated vaccine
May lose key antigens on attenuation
May develop virulent factors
Can infect immunocompromised
Can be out competed by other infections
Pros of live attenuated vaccines
can replicate - only low doses needed
strong immune response (life-long immunity)
can induce strong local immune response in site where particular infection is most likely to occur (LAIV)
Dead pathogen vaccines
Example: Influenza split vaccine, Hepatitis A
Description: Organism is grown and then killed either chemically (e.g with phenol or formaldehyde) or by heating
Mechanism: Antigenic components still intact so can stimulate B cell and T cell responses
Pros of dead pathogen vaccines
Effective
Cheap
Simple
Cons of dead pathogen vaccines
Antigen can be altered or destroyed in inactivation
Live pathogen needed to grow (risky for influenza)
live pathogen can contaminate vaccine (polio)
vaccine induced pathogenicity is a risk
Recombinant protein vaccines
Example: Hep B surface antigen (HepBsAg)
Description: recombinant protein from antigen (cultured in yeast)
Mechanism: immune system will generate neutralising antibodies against the antigens
Pros of recombinant protein vaccines
Pure
safe
good immune response against targeted part of pathogen
low strain variation
Cons of recombinant protein vaccines
Expensive
protein structure may not be exactly the same (post-translational modifications may be absent)
Conjugate vaccines
Example: S. pneumoniae, HIB
Description: Polysaccharide coat component is coupled to an immunogenic “carrier” protein
Mechanism: Protein stimulates a T cell response (via CD4) which improved B cell immune response (T cell helps affinity maturation to take place)
Pros of conjugate vaccines
improves immunogenicity
highly effective against infections caused by encapsulated bacteria
Cons of conjugate vaccines
Expensive
strain specific
carrier protein may interfere with immune response
Adjuvant
substance used in combination with specific antigen that produces a more robust immune response than the antigen alone
How do adjuvants stimulate a more robust immune response?
-Potentiate immune response by interacting with PAMPs and DAMPs (cause cell to release inflammatory mediators)
-Recognised by pattern-recognition receptors on dendritic cells
-which present antigens to T cell
Reasons for new vaccines (5)
Changing (aging) Demographics
Changing Environment (Dengue/other arboviruses)
New diseases (COVID-19)
Old diseases that still cannot be fixed (HIV/TB/Malaria)
Antibiotic Resistance (MRSA, all bacteria)
Barriers to vaccine production
Scientific challenges
Injection Safety
Logistics/Cold chain
Development issues - time, cost of vaccine development is high, cost of product
Public expectation of risk-free vaccines
How does vaccine development success rate depend on antigen variability?
more diversity = less protective
classic immune memory will only recognise one antigenic strain
therefore vaccine antigens need to cover all the variety
In the event of a new virus outbreak, what is used to limit spread?
Administration of synthetic/humanised antibodies against virus = gives short term protection against virus
Adaptive transfer of antibodies
act of administering protective antibodies (either synthetically produced or humanise after being harvested from animals) to individuals to prevent infection
