Lec 14- Immunotherapy II Flashcards
Active immunisation
- The deliberate induction of an immune response
- To use the natural immune defence to provide long term protection against infection
- Sometimes known as ‘Vaccination’
Primary versus 2ary
1) In primary response the number of Abs per ml of serum
2) 2ry response memory cells to the Ag so response is quicker and more cells per ml of serum (more severe)
Course of an infection
1) Establishment of infection (gradual increase)
2) Induction of adaptive immune response (rapid increase to a peak)
3) Adaptive immune response (gradual decrease in microbe number till eradication)
4) immunological memory (acquired immunity)
- Adaptive immunity prevents reinfection
- Immunisation removes the need for infection to obtain memory
Vaccination
-Stimulate our body to develop SPECIFIC immunity
-Protection and memory
-When we encounter a pathogen qe respond
+rapidly
+effective
+via secondary immune response
Immuno-conversion to vaccine
-Not all people respond strongly
-No vaccine is 100% effective
-No problem
-Herd immunity
+Chance of an infected person containing a non-immune person is low because so many people are vaccinated (TB)
Risk benefit assessment- MMR vaccine
- Successful vaccination programmes rely upon engagement/compliance
- If people perceive a low disease risk (unlikely to get it; not severe if they do) then they worry about risks
- Risk of adverse reaction perceived worse than risk from the disease
Measles outbreak
- Discredited link between MMR and autism
- Vaccination rates dropped (<85%)
- Herd immunity lost (95% needed)
- 1/10 with measles
UK measles Data
-2006 1st measles death for 14 years
Features of effective vaccine
1) safe- vaccine must not itself cause illness or death
2) Protective- vaccine must protect against illness resulting from exposure to live pathogen
3) Gives sustained protection- Protection against illness must last for several years
4) Induces neutralising Ab- some pathogens (polio virus) infect cells that cannot be replaced (neurones). Neutralising Ab is essential to prevent infection of such cells
5) Induces protective T cells: Some pathogens, particularly intracellular are more effectively dealt with by cell-mediated response
6) Practical considerations: Low cost per dose; biological stability; ease of admin; few side effects
Vaccine types
- Live, attenuated vaccine
- Inactivated vaccine
- Toxoids
- Sub unit vaccine
Polio has 2 vaccines
- Polio Sabin vaccine is the live attenuated vaccine
- Polio Salk vaccine is inactive or killed
- There are 2 vaccines
Live attenuated
-Attenuation
+to weaken
+Reduced pathogenicity of microbe
-Grow organism under abnormal conditions
+Grow virus in non-human cells (by adapting to infect monkey cell, if we then introduce back to a human it is not able to work well)
-The pathogenic virus is isolated from a patient and grown in human cultured cells
-The cultured virus is used to infect money cells
-The virus acquires many mutations that allow it to grow well in monkey cells
-The virus no longer grows well in human cells (it is attenuated) and can be used as a vaccine
Variolation
-15th C- recorded attempts of immunisation
-1718 Lady Mary Wortley Montague
+Variolated her own children
+Inhaled dried crusts of pustules (they drying weakens the virus so she attenuated)
-Protected from variola
Edward jenner
-Milk maids resistant to small pox
-Late 18th Century
-Cowpox (Vaccinia virus)
+Disease of cows (Zoonotic in humans)
+Poorly pathogenic in humans
+Protects human from small pox
+Cowpox has the same Ag
-Natural attenuation
1967: WHO global campaign to eradicate smallpox
-The Soviet Union first suggested a global effort and donated >80% of vaccine needed
-A freeze-dried vaccine employed
+Storable without refrigeration
+(1 month stability)
-This was delivered with a bifurcated needle (Low dose and could be sterilised)
Attenuation
-Abnormal culture
+BCG strain of M.bovis doesn’t cause TB but has preserved Antigenicity (has Ag)
+Variable protection offered (0-80%: Malawi UK)
+Schedule of immunisation is now risk-based
-Genetic modification
+More rapid and reliable than above
1) Isolate pathogenic virus
2) Isolate virulence gene
3) Mutate virulence gene and delete virulence gene
–> resulting virus is viable, immunogenic but avirulent. It can be used as a vaccine
Live attenuated- Advantages
-Most anti-viral vaccine currently \+Induce strong immune responses \+Promotes life-long immunity -Can induce more effector mechanisms \+E.g. Tc cells -Killed virus vaccines \+No-replication --> no intracellular proteins \+No MHC I present -_> No Tc generation
Live attenuated- Disadvantages
Risk of reversion
-Type 3 sabin vaccine (OPV) differs at 10 of 7429 nt -> Neurovirulent strain (Vaccine-induced disease (risk 1 in 2.4x106) this means that this risk is very high
Can cause diseases
-Young, old, immune-suppressed
Vaccinated people can transmit the attenuated vaccine organism
Storage problems- Liquid is hard to keep stable
Salk and Sabin
- Because the Salk vaccine is so close to the actual virus there a large amount of reversion
- This means that in a relatively large amount of vaccines you are introducing normal virus (due to reversion) meaning we would really never get rid of it
- Eradication using the attenuated (OPV) Sabin is unlikely
- Return to IPV (Salk) vaccine
Success in India
- As recently as 2009, India had more cases of polio than the other 3 (Afghanistan, Pakistan and Nigeria) combined
- But it has not seen as a case since 2011. These results show that success against polio can be achieved in challenging circumstances
Inactivated/Killed
-Suspension of intact microbes
-Generated by physical or chemical means
+Heat (Affects Ag- not great)
+Formaldehyde
(Used for Polio IPV Salk vaccine)
-Still immunogenic
Inactivated or Killed Advantages or disadvantages
\+ No risk of reversion \+Easily stored \+Highly stable -Varibale efficiency -Generate weaker response ] -Boosters needed
Toxoid
-For diseases caused by exotoxins \+Diphtheria (Corynebacterium diphtheriae) \+Tetanus (C.tetani) -Toxin purified and inactivated \+Physical or chemical means \+Complete detoc needed W/o loss of epitope structure (otherwise won't be the same Ab produced that would clear toxins) -Toxoid can still seroconvert \+Neutralising Abs
Sub-unit vaccine
-Avoids use of whole pathogens
-Immunise with key components of the pathogens
+Alone they don’t cause disease
+Response to them protects
-Streptococcus pneumoniae –> pneumonia
+Polysaccharide from capsules inhibit phagocytosis
+Poor at stimulating
+Pneumococcal polisaccaride vaccine (PPV)
+Pneumococcal conjugate vaccine (PCV)
Polysacc conjugated to a protein to improve effectiveness (thymus-dependant Ag)
Peptide vaccines
-Reductionist
-Vaccinate with part of a protein
-Problems
+Peptides are short and don’t fold
+Reduced ability of Abs to bind due to loss of conformation
+Poor at humoral stimulation
-Provides relatively effective hepatitis B vaccines
-Recombinant peptides can be used (synthetic)
DNA Vaccine
- A surprise
- Insert cloned DNA for a gene
- Animals respond B and T to the encoded protein
- DC- dependant
1) clone gene for influenza hemagglutinin in a plasmid
2) Injected cloned gene into muscle tissue
3) Infect mice with influenza virus
4) Measure virus titer
Considerations
-Administration \+Route can be crucial \+i.m. injection may not protect so well against infection at mucosal surfaces \+You must induce protection at relevant site -Salk Injection (IPV) \+Injectedable, killed -Sabin OPV \+Oral, live, attenuated -Induction of mucosal immunity required \+Oral-faecal spread
Adjuvants
-Non-specifically enhances immune response to Ag with which it is mixed
-Used for non-living vaccines
Must be: Safe; bio-degradable; Stable; Chemically defined; efficient
Act in 2 ways
-Activate the responding cells of the immune system
-Alter the delivery by affecting the rate or route of delivery
e.g. promote DC involvement and delivery to local draining lymph nodes
Challenges
-Mutating pathogens \+Influenza \+HIV -New and re-emerging disease \+TB \+SARS \+New coronavirus \+Zika -Compare parham figures
