Lecture 25; Vaccines Flashcards
Whats a vaccination that cannot be given until 15 months of age?
MMR
This means theres a portion of the population very young that is unprotected.
What are some diseases that cannot be vaccinated against yet, that are rampant?
Tb
Malaria
Respiratory disease
What is the principle of vaccinations?
Subject is given attenuated live organisms or components of the organisms or recombinant product.
This stimulates the immune system to produce antibodies and a memory response (boosters to enhance this.)
Therefore can meet the pathogen again and not have a response or a very mild one.
How long does it take for the non-vaccinated immune system to develop an antibody response to a pathogen?
Primary response ~7 days, peak around 14 days.
Secondary response much more rapid and far stronger. (Higher affinity ABs)
Whats an adjuvent in vaccines?
Something added to enhance the immune response and signal that there is danger.
What are some examples of successful immunisation campaigns?
Measles Mumps Rubella Polio Diphtheria Pertussis
What is the common mechanisms of successful vaccinations?
Induction of high affinity neutralising antibodies
Rapidly bind to pathogen
Prevent attachment/entry into host cells
What are the characteristics of a good vaccine?
Efficacy
Safety
Pathogen
What characteristics make a vaccine have good efficacy?
- T cell dependent response (important for polysaccharide vaccines, as under 2 cant respond to these)(protein+polysc conjugation gets around this)
- Elimination (of pathogen, so cant carry it asymptomatically)
- Protection
- Memory
- High uptake (80 – 90%)
What makes a vaccine safe?
- No risk of causing disease
* Side effects no worse than natural disease symptoms
What makes a good pathogen for a vaccine?
- Acute rather than chronic disease
- Induces immunity upon natural exposure
- Undergoes little antigen variation
- Does not attack immune system cells
- No animal or environmental reservoir
What are some features that make a vaccine effective, in terms of immune system regulation?
- Induces neutralizing antibodies
- some pathogens i.e polio infect cells that can to replaced i.e neurons therefore critical to neutralise them
- Induces Protective T cells
- IC pathogens must be dealt with by cellular mechanims
What are some practical considerations for vaccinations?
- low cost
- biologically stable
- ease of administration
- Few side effects
Whats a challenge to vaccine uptake?
• ~75% uptake required for herd immunity
• No personal experience of once common diseases
• Popular media emphasise vaccine risks – lose sight of the enormous benefit
-1970’s: UK, Pertussis Vaccine
-1990’s: UK, Measles Vaccine
Whats defines a successful vaccine?
Successful vaccine:
stimulates an effective immune response to target antigens without itself causing disease
What does attenuating a vaccine mean?
- Growth in vitro can lead to loss of virulence (ability to replicate in humans)
- This definition Extended to use of killed/inactivated organisms
What are some examples of attenuated pathogens used in vaccines?
• Examples:
– Live: smallpox, BCG, measles, mumps, rubella, oral polio
– Inactivated: typhoid, plague, cholera, Hep A, polio
– Subunit: anthrax, tetanus
What are the most common toxoid vaccines (vaccines that use toxins)?
• Combined diphtheria/tetanus/pertussis vaccine (DTaP)
What are subunit vaccines?
• Subunit vaccine
– Chemically inactivated toxins or toxoids from each bacterium
– Retain antigenic properties
– Vaccination stimulates neutralising antibodies to the toxins
What are some new developments in vaccines?
- Better defined adjuvants
- Better strategies for identifying antigens
- Improved manufacturing processes
- Vaccine delivery vehicles
- Alternative delivery routes (mucosal vs intramuscular)
- Response to emerging pathogens
What is the modern approach to vaccine development?
Recombinant technology
> Obviates need to work with pathogenic material
What is an aim of new vaccine development?
- Use conserved epitopes that are associated with protective immunity
- Downside with using more complicated epitopes is that there is the potential for autoimmune diseases or less specific immune response than wanted.
What are the Limitations of purified recombinant antigen vaccines?
Highly purified/defined vaccines do not always fully recapitulate the immune response to a natural infection
e.g. Pertussis vaccine: rapid waning of protective immunity; fails to prevent colonisation and transmission
What are some better adjuvents?
TLR3 activating adjuvents (flu vaccine)
TLR5 activated by flagellin
Modified bacterial toxins: e.g. CT, LT
What is reverse vaccinology?
Genome sequence of target pathogen
In silico prediction of vaccine candidate antigens (make sure theyre not similar to human proteins) Refine the parameters until a very specific protein can be sued for vaccination that produces an immune response highly specific to that pathogen
What is currently being done for flu vaccines?
Synthetic production of vaccines and culture use.
Use of non-pathogenic bacteria to deliver vaccine antigens
