vaccines

Question 1

what are the two types of immunisation?

Answer 1

passive
active

Question 2

describe passive immunisation

Answer 2

The administration of pre-formed “immunity” from one person or animal to another person

Question 3

what are the limitations of passive immunisation?

Answer 3

Only humoral (antibody) mediated
(not work if cell mediated!)

Question 4

what are the advantages for passive immunisation?

Answer 4

Gives immediate protection
Effective in immunocompromised patients

Question 5

what are the disadvantages for passive immunisation?

Answer 5

Short-lived
Possible transfer of pathogens
“Serum sickness” on transfer of animal sera

Question 6

2 examples of passive immunisation

Answer 6

1. Human Normal Immunoglobulin (HNIG)
2. Convalescing Serum ( SARS CO-V2

Question 7

What are the three approaches to making a vaccine?

Answer 7

1. inactivated vaccine
2. Live attenuated vaccine
3. Viral vector vaccines

Question 8

how do non living vaccines work?

Answer 8

Non-living vaccines do not cause infection, but the antigens contained in it induce an immune response that protects against infection – by non-self antigen recognition.
Non-living vaccines can also be cell-free toxoids - inactivated toxins

Question 9

problems and limitations with vaccines

Answer 9

• The organisms must be grown to high titre in vitro (viruses and some bacteria difficult/expensive to grow in the lab)
• Whole pathogens can cause excessive reactogenicity (i.e., adverse reactions, excessive immunological responses)
• Immune responses are not always close to the normal response to infection, e.g., no mucosal immunity, no CD8 Tc responses
• Usually need at least 2 shots

Question 10

examples of bacteria used in vaccines

Answer 10

diphtheria -formaldehyde treated toxin - rendered a non-toxic “toxoid
tetanus - texoid as above
pertuissis- whooping cough
cholera- heat killed bacteria

Question 11

examples of viruses used in vaccines

Answer 11

Polio vaccine (Salk) - inactivated virus-IPV
Influenza vaccine - inactivated virus
Hepatitis A vaccine - inactivated virus
Rabies vaccine - inactivated virus
SARS-Co-V2 (Valneva) - inactivated virus

Question 12

what are live attenuated vaccines?

Answer 12

The organisms replicate within the host and induce an immune response which is protective against the wild-type organism but does not cause disease.

This is more real-life and provides better protection

Question 13

define attenuation

Answer 13

Where an organism is cultured in such a way that it does not cause disease when inoculated into humans.

It has lost its pathogenicity but retains its antigenicity – (i.e., shape).

Question 14

advantages to live attenuated vaccines

Answer 14

Immune response more closely mimics that following real infection because its not fixed – no shape change.

Better immune response so lower doses are required, so the scale of in vitro growth needed is lower.

Route of administration may be more favourable (oral).

Fewer doses may be required to provide protection.

Question 15

problems and limitations with live attenuated vaccines

Answer 15

• Often impossible to balance attenuation and immunogenicity
• Reversion to virulence
• Transmissibility
• Live vaccines may not be so attenuated in immunocompromised host

Question 16

2 examples of bacterial live attenuated vaccines

Answer 16

• Bacille Calmette-Guérin (BCG) Mycobacterium bovis grown over many passages in vitro. Gives some protection against TB (tuberculosis)
• Salmonella typhi - temperature sensitive strain given orally.

Question 17

examples of viral live attenuated vaccines

Answer 17

• 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 as MMR

Question 18

give examples of pathogens lacking vaccines

Answer 18

HIV, malaria, Schistosomiasis, Leishmania spp, Herpes Simplex Virus, CMV, RSV, Rhinoviruses, Group B streptococci, Meningococcus group B, M. leprae…….

Question 19

why are there so many pathogen lacking vaccines?

Answer 19

-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.

Question 20

what are the novel vaccine approaches?

Answer 20

• Recombinant Proteins
• Synthetic Peptides
• Live Attenuated Vectors
• mRNA Vaccines
• Polysaccharide-Protein Conjugates

Question 21

what are recombinant proteins?

Answer 21

Genetically Engineered and produced from bacteria, yeast, insect or mammalian cells

Question 22

advantages of recombinant proteins

Answer 22

Avoid the problem of having to grow pathogen in vitro

Question 23

disadvantages of recombinant proteins

Answer 23

Major difficulties are finding a protein or proteins that are protective and generate a strong enough immune response

Question 24

examples of recombinant proteins

Answer 24

Hepatitis B Surface Antigen
HPV vaccines Cervarix and Gardasil (HPV16 and 18)
SARS-Co-V2 – Novavax (recombinant spike protein produced by moth cells in culture, these are purified, assembled into a synthetic nanoparticle for injection – 14 spike proteins per particle)

Question 25

what are synthetic peptides

Answer 25

Peptides synthesized directly using a machine - avoids the need for pathogen growth

Question 26

problems with synthetic peptides

Answer 26

• Identifying protective epitopes
• Inducing a strong response
• Inducing a broad response

Question 27

what are live attenuated vectors?

Answer 27

-Composed of a safe living attenuated viruses that have inserted genes encoding foreign antigens, which are displayed to the immune system.

Question 28

what are DNA vaccines?

Answer 28

a mammalian plasmid containing DNA that encode for the foreign protein ( yellow) of interest is injected directly

Question 29

how are DNA vaccines made?

Answer 29

This requires a lipid nanocarrier to get the DNA into a human cell. The DNA goes to the nucleus, gets transcribed and the foreign protein expressed with MHC to stimulate the immune response

Question 30

advantages of DNA vaccines

Answer 30

-Avoid the need to grow the pathogen, viral vector
* No live organism involved
* DNA is cheap to produce

Question 31

disadvantage of DNA vaccines

Answer 31

• Problem is often poor immunogenicity
• None on the market

Question 32

how are mRNA vaccines made?

Answer 32

-mRNA of the target foreign protein is synthesized in vitro. It is complexed with lipid nanoparticles that stabalise and protect the mRNA from degradation and allow the mRNA to cross the plasma membrane.

The mRNA is translated in the
cytoplasm and the protein presented
on the surface of the cell with MHC
Stimulating the immune response.

Question 33

advantages of mrna vaccines

Answer 33

• Avoid the need to grow the pathogen, viral vector
• No live organism involved
• mRNA is relatively cheap to produce
  -Quick to make new variations of vaccine

Question 34

what are t independent antigens

Answer 34

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

Question 35

recent changes to the vaccination programme

Answer 35

The addition of a pneumococcal conjugate vaccine (PCV) at 2, 4 and 13 months of age;

A dose of MenC vaccine at 3 and 4 months;

A booster dose of Hib and MenC vaccine (given as a combined Hib/MenC vaccine) at 12 months of age.

HPV vaccine for teenage girls and boys soon

BCG no longer routinely given to teenagers. Targeted on at risk infants.