Vaccine Platforms

Question 1

outline the different vaccine platforms

Answer 1

1. live (attenuated)
2. killed (inactivated)
3. purified proteins ( including Mabs) and toxoids
4. recombinant proteins
5. virus like particle
6. polysaccharide
7. glycoconjugate
8. viral vector
9. mRNA vaccines

Question 2

what are monovalent vaccines

Answer 2

designed to immunise against a single antigen or single microorganism

Question 3

what is a multivalent vaccine

Answer 3

designed to immunise against 2 or more strains/isolates of the same microorganism

Question 4

what is a combination vaccine

Answer 4

designed to immunise against multiple organisms

Question 5

what is a heterologous vaccine

Answer 5

confers protective immunity against a pathogen that shares cross reacting antigens with the micro-organisms in the vaccine

Question 6

what are the properties of inactivated vaccines

Answer 6

1. virus/bacteria grown in culture
2. organism inactivated physically (heat, radiation) or chemically (formalin)
3. test for inactivation before use
4. usually no cold chain

Question 7

what are the properties of attenuated vaccines

Answer 7

1. virus/bacteria repeatedly passaged in cells or chick embryos until virulence lost
2. or genome specifically modified
3. test for virulence before use
4. requires cold chain
5. attenuation due to mutation of specific genes when cultured in non human cells

Question 8

compare the safety between inactivated and attenuated vaccines

Answer 8

• killed- safe, cannot revert to virulence
• attenuated- target groups only, potential for infection

Question 9

compare the stability between inactivated and attenuated vaccines

Answer 9

1. killed- stable, may not require cold chain
2. attenuated- varies, often requires cold chain

Question 10

compare the target groups between inactivated and attenuated vaccines

Answer 10

1. killed- all ages and can use in immunosuppressives
2. attenuated- mature immune system only and less use in immunosuppressives

Question 11

compare the response between inactivated and attenuated vaccines

Answer 11

killed has a weaker response than attenuated

Question 12

compare the dosage between inactivated and attenuated vaccines

Answer 12

1. killed- multi dose and booster, parenteral
2. attenuated- fewer doses, oral

Question 13

compare the modifications between inactivated and attenuated vaccines

Answer 13

1. killed- purified protective antigens
2. attenuated- genetic modifications

Question 14

give an example of an attenuated vaccine

Answer 14

oral polio vaccine (OPV)

Question 15

give an example of an inactivated vaccine

Answer 15

inactivated poliovirus vaccine (IPV)
- chemically inactivated

Question 16

what are the 2 types of purified protein vaccines

Answer 16

1. natural protein antigen purified from the bug itself
   - eg. inactivated diphtheria and tetanus toxoids
2. recombinant protein antigen created by genetic engineering and produced in an expression system
   - eg. recombinant Hep B surface antigen produced in yeast

Question 17

describe how toxoids are produced

Answer 17

1. pathogenicity of some bacteria lead to secreted bacterial toxins
   - exotoxins
2. exotoxins induce T h 2 type response but cannot be used as vaccines
   - inactivated by treating with formalin
3. inactivated toxins= toxoids
   - safe to use for vaccines
4. can be created by genetic engineering

Question 18

what occurs with immunisation with toxoids

Answer 18

1. creates memory B cells
2. on recall, B cells produce neutralising antibodies

Question 19

what is the mechanism of action of toxoids

Answer 19

toxoid specific neutralising antibodies bind to and complex the bacterial toxins, inactivating them

Question 20

what is ronapreve

Answer 20

1. two neutralising mAbs
2. binds to 2 different sites on the SARs-COV-2 spike protein, neutralising the virus’ ability to infect cells

Question 21

what are subunit vaccines

Answer 21

specific antigen/epitopes that induce potent and specific protective humoral or CTL responses
- example of recombinant proteins

Question 22

how are subunit vaccines manufactured once key antigens/epitopes are identified

Answer 22

1. chemical fractionation of intact microbe
   - purification and stabilisation of key antigens
   - chemical linkage of antigens
2. if key epitopes known, manufacture as peptides
   - 3d amino acids created using scaffolds
3. using recombinant DNA technology, genetic construct coding for antigen is conducted and express as soluble proteins/glycoproteins
   - recombinant subunit vaccines

Question 23

describe the case of bordetella pertussis

Answer 23

1. used for whooping cough in children
2. whole cell vaccine (killed)- effective but serious side effects
   - redness, pain and swelling at injection site
3. infanrix hexa now used- reduced side effects

Question 24

give an example of a vaccine using virus like particles

Answer 24

Gardisil
- a HPV vaccine
- prevents HPV binding to cell surface entry receptors on epithelial basal cells and induces high serum HPV type specific neutralising antibodies

Question 25

what is the major antigen in HPV

Answer 25

L1 capsid protein - expressed as a recombinant protein in yeast cells - L1 protein spontaneously assembles into 3d virus like protein - cannot cause disease and mild side effects

Question 26

what are polysaccharide vaccines

Answer 26

1. have a capsule layer around them and composed of polysaccharides 2. polysaccharide is highly antigenic- used as vaccines 3. polysaccharide is sugar not protein antigens - immune response is T cell independent 4. provide little protective immunity to infants/young children as they can't induce T cell independent humoral responses or create memory cells

Question 27

give examples of encapsulated bacteria

Answer 27

- neisseria meningitidis - streptococcus pneumonaie - haemophilus influenzae

Question 28

give an example of a polysaccharide vaccine and what it is used for

Answer 28

pneumovax 23- capsule components from 23 pathogenic serotypes of streptococcus pneumoniae - routinely offered to elderly patients - not recommended for children >2

Question 29

describe the structure of glycoconjugate vaccines

Answer 29

1. formed by chemically coupling the polysaccharide capsular antigens from Neisseria meningitidis, haemophilus influenzae or streptococcus pneumoniae to a carrier protein 2. carrier protein is toxoid from tetanus or diphtheria organisms

Question 30

give an example of a glycoconjugate vaccine

Answer 30

- Hib conjugate vaccine - DTaP/IPV/Hib - infanrix hexa - meningococcal ACWY vaccine

Question 31

give examples of new viral and bacterial vaccines introduced into clinic

Answer 31

1. viruses: Zika (phase II), HIV (phase III) 2. bacteria: typhoid conjugate vaccine (phase III)

Question 32

what are viral vector vaccines

Answer 32

1. use genetically modified viruses that are not pathogenic as vectors to get heterologous genetic material into a cell 2. this material encodes for pathogen antigens 3. once inside the cell, the viral genes produce new chimeric non pathogenic viruses or just pathogen antigens 4. APCs then process these to generate adaptive immunity

Question 33

give examples of viral vectors

Answer 33

- measles virus - adenovirus

Question 34

what are mRNA vaccines and how are they used

Answer 34

1. prime immune system which is then boosted by a viral vector - eg. Covid mRNA vaccine