Vaccines

Question 1

Variolation

Answer 1

[deliberate infection with smallpox]

Dried smallpox scabs were blown into the nose of individual who contracted mild form of disease

Upon recovery, they were immune to smallpox

Between 1-2% of those variolated died as compared to 30% when they contracted the disease naturally

Question 2

NO mass vaccination

Answer 2

each host in contact with infected host becomes infected (with a certain probability)

Question 3

WITH mass vaccination

Answer 3

outbreak attenuated/averted by lack of susceptible hosts

Question 4

heard immunity threshold

Answer 4

when the proportion of immune individuals in a population reaches threshold, the spread of disease to non-immune population can be interrupted

Question 5

concept of vaccinology

Answer 5

When exposed to a pathogen for the first time, we have no specific IgG antibodies against the pathogen -> infection can progress to disease

Over time, we produce antigen specific IgG antibodies i.e. memory immune response

Next time we’re exposed to this pathogen, we will be protected from the disease

If we were exposed to a pathogen that didn’t progress to a disease, then our bodies response would simply the generation of immune memory

Question 6

Basic concepts of vaccines

Answer 6

Deliver to body some part/all of disease organism that imitates the pathogen but isn’t pathogenic

Both bacteria and viruses contain antigenic components that can be suitable for generating vaccines

Question 7

types of vaccines

Answer 7

1. Live-attenuated vaccines - e.g. measles, mumps, rubella
2. Inactivated - e.g. hepatitis A, influenza
3. Recombinant sub-unit - e.g. hepatitis B
4. Toxoid - e.g. tetanus
5. Conjugate polysaccharide-protein - e.g. meningococcal

^ a single disease may have vaccines from several types

Question 8

Live-attenuated vaccines

Answer 8

Derived from disease-causing virus/bacteria

small dose given (enough to stimulate immune response)

immune response = identical to natural infection

Question 9

Live-attenuated vaccines - advantages/disadvantages

Answer 9

Cheap
Adjuvants not necessary

Potential to cause pathology
Stability

Question 10

Inactivated vaccines

Answer 10

Not alive and can’t replicate - can’t cause disease or infection even in an immunodeficient person

Dose administered by injection

First dose “primes” immune system; 2nd/3rd dose = protective immune response

Question 11

Inactivated vaccines - advantages/disadvantages

Answer 11

Generally safer
Easy to manufacture
Improved stability

Can be costly
Hypersensitivity

Question 12

Recombinant sub-unit vaccines

Answer 12

Comprised of one antigenic part of pathogen

Unique type of inactivated subunit vaccine that is composed of long chains of molecules that make up surface capsule of certain bacteria

Immune response to a pure polysaccharide vaccine = T-cell dependent
- Able to stimulate B cells without assistance of T-helper cells

DNA vaccines = type of recombinant vaccine

Question 13

Toxoids vaccines

Answer 13

Toxins = major virulence factors for some bacteria which cause disease

Toxoids = forms of chemically altered toxin that are no longer pathogenic

Antibodies produced in the body neutralise toxic moiety produced during infection rather act upon organism itself

Question 14

Toxoids vaccines - advantages

Answer 14

Highly efficacious

Safe

Question 15

Conjugate polysaccharide vaccines

Answer 15

Prepared from extracted cellular fractions

As carbohydrates don’t illicit T-cell response, the polysaccharides are often chemically attached to a carrier protein (often toxoids)

Question 16

Monovalent vaccine

Answer 16

designed to immunise against a single antigen/pathogen

Question 17

multivalent vaccine

Answer 17

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

Question 18

vaccine production - live attenuated vaccines

Answer 18

Pathogen passaged many times under stress conditions

Stress conditions pressure the virus to replicate differently
- Slower replication
- Loss of virulence factors

Causes virus to be attenuated -> no longer disease causing

Virus then purified and formulated

Question 19

vaccine production - inactivated vaccines

Answer 19

Whole pathogen grown and killed - heat/chemical modification (formaldehyde)

Question 20

vaccine production - Recombinant sub-unit vaccines

Answer 20

Identify sub-unit being targeted

Insert pathogenic gene into host-organism for production

Express protective antigen in safe easy-to-grow organism

Purify antigenic sub-unit and formulate

Question 21

vaccine production - Toxoid vaccines

Answer 21

Toxins are isolated from pathogen and purified

Toxins converted to toxoids (inactivated toxin) by chemical treatment

Toxoid then formulated

Question 22

vaccine production - conjugate polysaccharide vaccines

Answer 22

[Phase I]

• Surface polysaccharide from pathogen is grown (fermentation) and isolated
• Carrier protein is grown up separately and purified

[Phase II]

• Any toxins on polysaccharide are chemically removed
• Carrier protein and polysaccharide are then covalently attached together (chemical crosslinking)
• “conjugate” then purified and formulated

Question 23

Formulation of vaccines

Answer 23

[Crucial for efficacy and stability]

1. Active components
2. Adjuvants
3. Antibiotics
4. Stabilisers
5. Preservatives
6. Trace components

Question 24

why do we need adjuvants?

Answer 24

1. Stronger and longer - enhance immune response
   
   • Promotes rapid, long-lasting and broad immunity
   • Improves immune memory
2. Antigen-sparing - to induce protective antibody responses with less antigen
3. Cross-reactive immunity - induce a “broader” immune response, directed against strains/subtypes not included in vaccine
4. Overcome weakened immunity - in elderly and immunocompromised individuals

Question 25

how do adjuvants work?

Answer 25

Slow antigen release - maintains antibody levels

Inflammatory response - stimulates DC maturation; better utilisation of antigens; induction of CD4+ (Th1)

Immunostimulation