Vaccines Flashcards
What are the three types of vaccines used?
Whole-killed, toxoid and live attenuated.
Immunisation can be…
Passive immunisation
Active immunisation or Vaccination
Define passive immunisation
The administration of pre-formed immunity from one person/animal to another person.
What are the limitation of passive immunisation?
Only humoral (AB) mediated - not work if cell mediated.
What are the advantages of passive immunisation?
Gives immediate protection.
Effective in immunocompromised patients.
What are the disadvantages of passive immunisation?
Short-lived, possible transfer or pathogens - serum sickness:
Example of passive immunisation
Specific immunoglobulin (Ig)
- Human Tetanus Ig (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)
Human Normal Immunoglobulin (HNIG) (Passive immunisation)
Prepared from pools of at least 1000 donors, contains ABs against measles, mumps, varicella, hep a etc…
Convalescing serum (SARS Co-V2)
Pooled from people recovering from COVID-19 but clinical trial result suggests no overall increased efficacy against virus using passive immunisation.
Active immunisation
Non-living vaccines (whole killed and toxoids)
Live attenuated vaccines
The whole microbe vaccine
Bacteria or viruses grown in vitro and inactivated (formaldehyde or B-propionolactone)
Non-living vaccines do not cause infection - AG induced response that protects against infection - by non-self AG recognition.
Can also be cell-free toxoids - inactivated toxins.
Problems and limitations of whole killed vaccine
Organism must be grown to high titre in vitro (some cannot be grown in labs).
Whole pathogen can cause excessive reactogenicity (ADR)
Immune response are not always close to the normal response to infection.
Requires two shots.
Examples of bacterial whole killed vaccines
Diphtheria - toxoid (treated with formaldehyde)
Tetanus - toxoid
Pertussis - killed whole bacteria. Now acellular pertusses in the UK.
DTP given as one.
Cholera - heat killed bacteria.
Examples of viral whole killed vaccines.
Polio
Influenza vaccine
Hep A
Rabies
SARS-Co-V2
All inactivated viruses.
Live attenuated vaccines
Organism replicate within the host and induce an immune response which is protective against the wild type but does not cause disease.
More real life and provides better protection.
Attenuations
Cultured in such way that is does not cause disease when inoculated into humans.
Pathogenicity lost
Antigenicity retained
What are the advantages of live attenuated vaccines?
Immune response more closely mimics real infection - not fixed, no shape change.
Better immune response - lower doses.
Route of administration may be favourable (oral).
Fewer doses may be required.
What are the problems and limitations with live attenuated vaccines?
Impossible to balance attenuation and immunogenicity.
Reversion to virulence.
Transmissibility.
May not be attenuated enough for immunocompromised people.
Examples of bacterial live attenuated vaccines (ONLY 2)
BCG - TB
Salmonella typhi - temp. sensitive. Orally given.
Examples of viral live attenuated vaccines
Poliomyelitis (Sabin) - eradicate polio
Vaccinia virus - smallpox: cross reaction between itself and the variola virus.
MMR
Why are so many pathogens lack a vaccine?
Pathogen too difficult to grow
Killed pathogen not protective (shape change)
Impossible to obtain attenuated and suitably immunogenic strain
Too many strains causing disease etc.
List the novel vaccine approaches
- Recombinant Proteins
- Synthetic Peptides
- Live Attenuated Vectors
- mRNA Vaccines
- Polysaccharide-Protein Conjugates
Recombinant proteins
Genetically engineered - from bac, yeast, insect or mammalian cells.
Don’t have to grow pathogens in vitro.
Major issue: finding the proteins that are protective and strong enough to generate an immune response.
Examples:
HepB surface AG
HPV Cervarix, Gardasil
SARS-Co-V2 Novovax
Synthetic peptides
Directly uses a machine (no need to grow pathogens)
Problems:
Identifying protective epitopes
Inducing a strong + broad response
Viral vectors
Composed of safe living attenuated viruses that have inserted genes encoding foreign AGs which are displayed to the immune system.
Covid jab.
How do viral vectors work?
When injected the virus is taken up by an APC, the viral DNA is released and enters the nucleus. The viral DNA is transcribed to mRNA and translated to a protein – some of this spike protein is presented with MHC II on the cell surface as a foreign antigen. This is recognised by T-cells and initiates an immune response to the spike protein.
The virus is replication deficient and can not replicate in human cells limiting its spread.
DNA vaccines
Mammalian plasmid containing DNA that encodes for the foreign protein of interest is injected directly.
Required a lipid nanocarrier to get DNA into human cell.
What are the advantages and disadvantages of DNA vaccines?
Adv: no need to grow pathogen or viral vector.
No live organism is involved
DNA is cheap to produce
Disadv: poor immunogenicity
None on the market
mRNA vaccines
mRNA of the target foreign protein is synthesized in vitro + lipid nanoparticle (protects from degradation) crosses plasma membrane.
Translated in cytoplasm and the protein is presented on MHC.
T-independent AGs
Bacterial capsular polysaccharides cannot be processed and 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
Haemophilus influenzae (conjugate vaccines - type B polysaccharide vaccine or 7-valent conjugate.
Neisseria meningitidis type C - polysaccharide-protein conjugate.
Streptococcus pneumoniae 23-valent polysaccharide vaccine or 7-valent conjugate.
At what ages is pneumococcal conjugate vaccine is given?
PCV at 2, 4, 13 months
Meningitis C is given at
3 and 4 months
Booster dose of Hib and MenC vaccine (combined) given at
12 months of age.
HPV vaccine for…
Teenage girls and boys…
BCG vaccine changes
No longer given routinely - targeted risk infants.
8 weeks old vaccinations
Diphtheria
Tetanus
Pertussis
Polio
Hib
HepB
MenB
Rotavirus (Oral)
12 weeks vaccinations
Diphtheria
Tetanus
Pertussis
Polio
Hib
HepB
Rotavirus
Pneumococcal conjugate vaccine PCV13
16 weeks vaccinations
DTP
Polio
Hib
HepB
MenB
One year old
Hib/MenC
Pneumococcal conjugate vaccine
MenB
MMR
Eligible paediatric age groups
Live attenuated influenza vaccine (nasal spray, single application in each nostril)
3 years and 4 months
Diphtheria
Tetanus
Pertussis
Polio
MMR
12 to 13 years old
HPV
14 years old
Tetanus
Diphtheria
Polio
Meningococcal ACWY conjugate
65 years old
Pneumococcal polysaccharide vaccine
65 years old and older
Inactivated influenza vaccine
70 years old
Shingles vaccine
