Immunisation Flashcards
Passive immunisation including limitation
The administration of pre-formed “immunity” from one person or animal, to another person
Limitation: antibody mediated
Immunisation
Passive
Active or vaccine
Advantages of passive immunisation
Gives immediate protection
Effective in immunocompromised patients
Disadvantages of passive immunisation
Short-lived Possible transfer of pathogens “Serum sickness” on transfer of animal sera
Passive immunisation: specific immunoglobulin examples
Human tetanus immunoglobulin (HTIG) -rapid protection of exposed individuals Human rabies specific Ig -used after exposure to rabies to give protection until vaccine becomes effective Human Hepatitis B Ig (HBIG) Varicella Zoster Ig (VZIG)
Passive immunisation: normal immunoglobulin (HNIG)
Prepared from pools of at least 1000 donors, contains antibody against measles, mumps, varicella,
hepatitis A etc.
Active immunisation (vaccination) divided into
Non-living vaccines (whole killed and toxoids)
Live attenuated Vaccines
Non-living vaccines
1st exposure (vaccination) -antibody response (IgM and IgG) -smaller Memory immune response -larger antibody response, mainly IgG -extremely rapid
Whole killed vaccines
Bacteria/ viruses grown in vitro & inactivated using agent such as formaldehyde or b-propionolactone
Non living vaccine does not cause infection, but antigens contained in it induce immune response which protects against infection
Non-living vaccines can also be cell-free toxoids-inactivated toxins
Problems and limitations of whole killed vaccines
Organisms must be grown to high titre in vitro
Whole pathogens often cause excessive reactogencity
Immune responses not always close to normal response to infection, e.g no mucosal immunity, no CTL responses
Usually need at least 2 shots
Non-living vaccines
Bacterial or viral
Bacterial non-living vaccines examples
Diphtheria-cell free formaldehyde treated toxin- rendered non toxic “toxoid”
Tetanus, toxoid, as above
Pertussis- killed whole bacteria, given with the two above as DTP. 3-doses. UK now moved to acellular pertussis (aP)
Cholera- heat killed bacteria
Viral whole killed vaccine examples
Polio vaccine (Salk)-inactivated virus-IPV
Influenza vaccine-inactivated virus
Hepatitis A vaccine-inactivated virus
Rabies vaccine-inactivated virus
Live attenuated vaccines
The organisms replicate within the host, and induce an immune response which is protective against the wild-type organism
Advantages of live attenuated vaccines
Lower doses are required, so the scale of in vitro growth needed is lower
Immune response more closely mimics that following real infection
Route of administration may be more favourable
Fewer doses may be required
Problems and limitations of live attenuated vaccines
Often impossible to balance attenuation and Immunogenicity
Reversion to virulence?
Transmissibility?
Live vaccines may not be so attenuated in immunocompromised hosts
Bacterial live attenuated vaccine examples
Only 2BCG- Bacille Calmette Guerin. Mycobacterium bovis grown over many passages in vitro. Gives some protection against TB
Salmonella typhi- temperature sensitive strain given orally.
Viral live attenuated vaccine examples
Poliomyelitis (Sabin)-widely used to bring polio to the brink of eradication
Vaccinia virus- used in billions of doses to eradicate smallpox due to cross-reactivity between itself and the variola virus
Measles, mumps and Rubella- 3 given together
Pathogens lacking vaccines
A lot, e.g.
HIV, malaria, Schistosomiasis, Leishmania spp, Herpes simplex Virus, CMV, RSV, Rhinoviruses, Group B streptococci, Meningococcus group B, M.leprae,
Why are there so many pathogens lacking vaccines?
Various reasons
- pathogen too hard to grow
- killed pathogen not protective
- impossible to obtain attenuated and suitably immunogenic strain
- too many strains causing disease etc.
Novel approaches
Recombinant proteins Synthetic peptides Live attenuated vectors DNA vaccines Polysaccharide-protein conjugates
Recombinant proteins
Produced from bacteria, yeast, insect or mammalian cells
•Avoid problem of having to grow pathogen in vitro
•Major difficulties finding a protein or proteins which are protective, and generating strong enough immune response.
•2 examples on market, Hep B surface antigen, and HPV vaccines Cervarix and Gardasil
Synthetic peptides
Avoid need for pathogen growth •Identifying protective epitopes a problem •Inducing strong response can be problem •Inducing broad response can be problem •No examples on market
Live attenuated vectors
Express protein from the pathogen in a vector which is known to be attenuated and safe, e.g
• Vaccinia
• BCG
• Adenovirus
None on market
Potential problems in immunodeficient people
Vaccinia virus
-Progressive vaccinia Occurred in about 1.6 people per million vaccinated during the smallpox eradication campaign. These were likely immunocompromised people
Live attenuated vectors
Attenuated, genetically stable vaccine Vector able to take additional Foreign DNA Insert DNA encoding protective Antigen of pathogen, e.g HIV
DNA vaccines
Express protein from pathogen in mammalian expression plasmid which is then injected, so protein is expressed • Avoid need to grow pathogen • No live organism involved • DNA cheap to produce • Problem is poor immunogenicity • None on market
Herd immunity
Around 80% vaccinated protects the other 20%
T independent antigens
Bacterial capsular polysaccharides cannot be processed + presented on MHC class II
-no T cell help
Antibody response of low magnitude
Low affinity
Predominantly IgM
Little or no boosting on secondary exposure
Infants respond especially poorly and are major target group for these vaccines
-e.g. Haemophilus influenzae
-neisseria meningitidis
-streptococcus pneumoniae
Conjugation of TI antigens to proteins
Hib polysacc specific B cells bind polysaccharide and internalise whole conjugate, including protein Polysaccharide cannot be processed, but protein is and peptides derived from it are expressed on cell-surface with MHC class II Polysaccharide specific B cell receives help from DT specific T cell Strong antibody response even in infants, including IgG
Conjugate vaccines
Neisseria meningitidis type C - polysaccharide-protein conjugate vaccine
•Streptococcus pneumoniae-23-valent polysaccharide vaccine or 7-valent conjugate
•Haemophilus influenzae type B (HiB)- Polysaccharide protein conjugate vaccine
Recent changes to the childhood immunisation programme
Addition of pneumococcal conjugate vaccine (PCV) at 2, 4 and 13 months of age;
A dose of MenC vaccine at 3 and 4 months;
Booster dose of Hib and MenC vaccine (given as a combined Hib/MenC vaccine) at 12 months
HPV vaccine for teenage girls
BCG no longer routinely given to teenagers. Targeted on at risk infants
Do vaccines work
Yes, almost eradicated some disases
Do vaccines work
Yes, almost eradicated some disases
Almost 100% change
