Scientific Basis of Vaccines

Question 1

explain why Edward Jenner did experiments and what they showed?

Answer 1

people that got cowpox never got small pox

Challenge dose – proves protection from infection

Concept of attenuation, prior exposure to agent boosts protective response

Cross-species protection – antigenic similarity

Question 2

how was eradication of smallpox possible?

Answer 2

1. No sub-clinical infections (no asymptomatic patients)
2. After recovery, the virus was eliminated - no carrier states
3. No animal reservoir (once u cleared it from humans, it couldn’t reappear from the environment)
4. Effective vaccine (live vaccinia virus)
5. Slow spread, poor transmission

Question 3

definition of a vaccine

Answer 3

contains materials from an organism that will actively enhance adaptive immunity

-produces an immunologically “primed” state the allows for a rapid secondary immune response on exposure to antigen

Question 4

role of a vaccine?

Answer 4

protects an individual from a serious disease, or reduces the rate of infection

protects the population via herd immunity (public health intervention)

Question 5

what is a consequence of herd immunity?

Answer 5

don’t generate natural boosting (when your immunity is boosted by diseases in the community)

means you have to keep vaccine rates and herd immunity high

Question 6

Types of immunity?

Answer 6

1. ACTIVE
   - natural exposure
   - acquiring an infection
   - vaccination
   - long effect
2. PASSIVE
   - antibodies from another source
   - short effect

Question 7

Immune responses to antigen?

Answer 7

PRIMARY EXPOSURE

5-7 days - antibody response
2 weeks for a full response

IgM —–> IgG switching
memory B and T cells

SECONDARY EXPOSURE

with prior exposure, it takes 2 days for a full protective response

Question 8

2 general principles of vaccine immune response?

Answer 8

1. Induce the correct type of immune response (antibodies, cell mediated immunity)

• infections that exist in gut/bloodstream, antibodies are sufficient because they bind to the external surface of viruses and neutralise them
• systemic infections (TB) that lives inside bacteria inside cells, antibodies won’t be effective as a vaccine antibodies cannot get inside cells: you’ll need T cell immunity.

2. Induce the immune response in the right place

• good protective immunity at your mucosal surfaces requires secretory IgA, T cells circulating are irrelevant
• systemic infection needs T cells and antibodies in the blood.

Question 9

vaccines - duration of protection?

Answer 9

short-term (travel) - antibody sufficient
long-term - memory essential

Boosters - natural, vaccines

Type of infection:
long incubation time - systemic measles
short incubation time - surface cholera

Difficult to induce long-lasting immunity at mucosal surfaces

Question 10

explain what the immune system is like after birth?

Answer 10

After birth there is a high incidence rate of infection until about 2 yrs, when it drops off

children under the age of 2 are immuno naïve and haven’t developed their full immune potential - poor at making antibodies against LPS

Question 11

why can newborns not be vaccinated?

Answer 11

Babies that are born have high levels of maternal antibodies (sIgA in milk)– baby has a level of immune protection while its being breastfed, and maternal antibodies can live for up to 6 months.

We cannot vaccinate newborns using live attenuated vaccines as they will just be neutralised by the mothers antibodies, so we need to wait until the antibody levels have dropped enough that the virus can survive in the baby and drive a protective immune response.

Question 12

nature of antigens?

Answer 12

can be monotypic or polytypic

monotypic is something like measles, which has very little antigenic variation across all the different types of measles – get it once and you will be protected

Polytypic organisms undergo massive antigenic variation (influenza virus). You may get 1 strain and get an immune response, but it gives you no protection against the next strain that comes along.

Question 13

antigenic variation leads to?

Answer 13

genetic diversity

Question 14

serology can differentiate what?

Answer 14

exposure from vaccination

Question 15

Types of Vaccines

Answer 15

1. Live, attenuated organism
2. Killed, whole organism
3. Sub-unit vaccines

Question 16

Live, attenuated organism

Answer 16

MMR, BCG, polio yellow fever, VZV
-doesn’t cause disease because its attenuated but can provide T-cell immunity

doesn’t need another boost/injection as it will survive in the body long enough to have a large immune response to give good protection.

Polio - vaccine given to children, mutated and caused a new virulent strain - adults became infected with polio via the babies nappies. Most countries now use a killed vaccine for polio.

risks: reversion, immunosuppressed means risk of persistent infection, foetal damage

Question 17

Killed, whole organism

Answer 17

pertussis, flu (old type), polio (Salk type), cholera, HepA

good protection, boosting required

multiple boosters will have to be given to achieve a good level of protective immunity.

risks: toxicity/allergy, autoimmunity, contamination

Question 18

Sub-unit vaccines

Answer 18

individual components:

    - proteins					
- toxoids	(diphtheria, tetanus)		
- peptides (synthetic)		
- polysaccharide

Polysaccharides are quite difficult to make as vaccines because they don’t drive a very good immune response in children under the age of 2 - has to be conjugated

Question 19

what is a toxoid?

Answer 19

a toxin that has been inactivated with formaldehyde - it is now antigenic and non-toxic, and can be used as a vaccine

when in the body, the toxoid stimulates antibodies and a protective immune response for when the toxin actually enters the body

tetanus, diphtheria

Question 20

Bacterial Capsular Polysaccharides as vaccines

Answer 20

poor antigens, no short term memory or T cell immunity

less immunogenic in children <2yrs, poor IgG2 responses

you can enhance immunogenicity by protein conjugation (toxoid + outer membrane protein)

conjugation links polysaccharide antigen to a protein carrier that the infant’s immune system already recognises, provoking an immune response

• protein recognised by BCR, making B cell clonally expand to give a high affinity antibody response
• antigen presentation on MHC class II, recognised by TCR.

gives long lasting immunity and response in kids

eg. MenC vaccine

Question 21

Adjuvants

Answer 21

chemicals or lipid structures that enhance the immune response using the vaccine components

• enhance immune response to antigen
• promote uptake and antigen presentation
• stimulate correct cytokine profiles