Vaccination and Immunisation

Question 1

Has smallpox been eradicated ?

Answer 1

Yes

Question 2

Define the Pasteur principle.

Answer 2

• ISOLATE pathogen
• INACTIVATE
• INJECT

Question 3

What are some of the vaccines we can expect in the coming years ?

Answer 3

Meningitis, Papilloma, Avian Flu

Question 4

What are the essential features of vaccines ?

Answer 4

♠ Must provide effective protection without risk of causing disease or severe side effects
♠ Should stimulate correct arm of immune response, ie antibodies or effector T cells (i.e. should stimulate same response as the actual disease, most of the time stimulate neutralising antibodies to prevent re- infection)
♠ Protection should be long-lived
♠ Stable for long-term storage and transport
♠ Economically affordable for widespread use

Question 5

Identify the main types of vaccines.

Answer 5

Live
Attenuated
Killed
Extract
Recombinant
DNA

Question 6

Describe the main features of live vaccines.

Answer 6

Organisms capable of normal infection and replication. Not used against pathogens that can cause severe disease.

Question 7

Describe the main features of attenuated vaccines + give examples of attenuated vaccines.

Answer 7

Organism is live, but ability to replicate and cause disease reduced by chemical treatment or growth-adaptation in non-human cell lines (e.g. measles, mumps, rubella).

Question 8

Describe the main features of killed vaccines + give examples of killed vaccines.

Answer 8

Organism killed by physical or chemical treatment. Incapable of infection or replication, but still able to provoke strong immune response (e.g. B.pertussis, typhoid)

Question 9

Describe the main features of extract vaccines + give examples of extract vaccines.

Answer 9

Materials derived from disrupted or lysed organism (e.g. capsular polysaccharides). Used when risk of organism surviving inactivation steps (e.g. flu, pneumococcal, diptheria, tetanus).

Question 10

Describe the main features of recombinants vaccines + give examples of recombinant vaccines.

Answer 10

Genetically engineered to alter critical genes. Often can infect and replicate but does not induce associated disease (e.g. HPV).

Question 11

Describe the main features of DNA vaccines.

Answer 11

Naked DNA injected. Host cells pick up DNA and express pathogen proteins that stimulate immune response

Question 12

What are the main risks associated with vaccines ?

Answer 12

Risk of allergic response: not a response to the vaccine itself, but to something with the vaccine (stabiliser, preservative). e.g. eggs

Question 13

Which type of vaccine is the best ? Why ?

Answer 13

-In general the most effective vaccines
have been live or attenuated
-Living or attenuated organisms express proteins and stimulate the immune response in a manner which most closely resembles normal infection

Question 14

What is the relationship between safety and effectiveness of vaccines ?

Answer 14

Paradoxically, the safer the vaccine, the

less effective some have been

Question 15

Define herd immunity.

Answer 15

The resistance to invasion and spread of an infectious agent in a group or community, based on the resistance to infection of a high proportion of individual members of the group (resistance is a product of the number susceptible and the probability that susceptibles will come into contact with an infected person)
i.e. If enough are vaccinated then the chances of an unprotected person meeting a pathogen becomes small. The population remain essentially resistant.

Question 16

What percent immunity coverage is usually deemed sufficient to produce herd immunity ?

Answer 16

95%

Question 17

What is the current evolution if vaccination rates ? What is the consequence of this ?

Answer 17

Vaccination rates have fallen because a) beneficial impact of vaccine so clear that some people no longer are aware of dangers of disease and b) public debate on whether side-effects occur (e.g. MMR)

Consequence is a pool of unimmunised individuals is created that can become victim to disease (measles more likely due to this).

Question 18

Identify the main current UK childhood vaccinations, and their components. How are they given ?

Answer 18

• DTaP/IPV/Hib: Diptheria, tetanus, pertussis, inactivated Polio vaccine, haemophilus influenzae type B
• Men C: meningococcal C conjugate
• DTaP/IPV: booster vaccine for diptheria, tetanus, pertussis, Polio.
• Td/IPV: booster vaccine for diptheria, tetanus, polio
• MMR (measles, mumps, rubella) two doses
• BCG: tuberculosis (now for at-risk individuals)
• MenACWY (teenagers + first year uni without previous vaccination)
All given by injection

Question 19

Identify the main post-childhood UK vaccinations. When is each of these given ?

Answer 19

• Pneumococcal: offered to 65yr and over individuals

* Flu: offered to elderly and at-risk individuals.

Question 20

Identify some of the advised vaccines when traveling.

Answer 20

Avian Flu, West Nile Virus, Marburg Virus, Poliomyelitis

Question 21

What is the issue with Meningococcus B vaccination ? How have we solved this issue ?

Answer 21

The capsular polysaccharide antigen that would normally be a good target looks almost identical to a sugar on NCAM, an important neuronal membrane protein. Antibodies could cause autoimmunity

BUT

Reverse vaccinology: whole bacterial genome sequenced, work out from this what potentially genes that pathogen can make, clone all those and express them individually. Then express proteins that derive from these genes, inject them in mice so we see response and therefore can find candidate aspects of the pathogen to vaccinate against (all in 24-36 months)

Question 22

What are the new diseases for which to expect vaccines in the coming years ? Where does each of these diseases originate from ?

Answer 22

→ HIV: nonhuman primate origin
→ SARS (Severe Acute Respiratory Syndrome): palm civets and racoon dogs (animal markets)
→ vCJD (Variant Creutzfeldt-Jakob disease): food chain, rendering

Question 23

Identify infectious diseases with decreasing incidence.

Answer 23

Polio
Diphteria
Cholera
Meningococcus C (in UK)

Question 24

Identify infectious diseases with persisting incidence.

Answer 24

TB
HIV
Malaria

Question 25

Identify emerging infectious diseases.

Answer 25

Avian influenza
SARS
MRSA (in UK)
vCJD
Ebola

Question 26

Explain the function of dendritic cells in infection, and how that is relevant to vaccination.

Answer 26

• Sit in mucosal surfaces controlling immune response (at the interface between innate immunity and specific immunity), sampling the environment looking for pathogens using surface receptors (especially Toll-like receptors, which include Pattern Recognition Receptors (PRR))
• TLRs can notable detect lipopolysaccharides and heat shock proteins (TLR4) dsRNA, lipopeptides, flagellin.
• Once they encounter an antigen, become activated and move from mucosal surfaces to lymph nodes, changing their surface receptors in that process
• Activation of DC’s vastly leads to increases their ability to capture and process antigen and immunogens, and also attract and activate T cells to become effector cells (i.e. initiate adaptive immune response)

• When inject a vaccine, include adjuvant in vaccine which will target one of these receptors and therefore massively activate the immune cells
• E.g. When CpG is included (as an adjuvant) with HepB or flu vaccines the result is increased antibody or IFN-γ secretion

Question 27

When are most of the important vaccines given during life?

Answer 27

Most of them are given in childhood in several boluses at several ages