Lecture 25; Vaccines

Question 1

Whats a vaccination that cannot be given until 15 months of age?

Answer 1

MMR

This means theres a portion of the population very young that is unprotected.

Question 2

What are some diseases that cannot be vaccinated against yet, that are rampant?

Answer 2

Tb
Malaria
Respiratory disease

Question 3

What is the principle of vaccinations?

Answer 3

Subject is given attenuated live organisms or components of the organisms or recombinant product.

This stimulates the immune system to produce antibodies and a memory response (boosters to enhance this.)

Therefore can meet the pathogen again and not have a response or a very mild one.

Question 4

How long does it take for the non-vaccinated immune system to develop an antibody response to a pathogen?

Answer 4

Primary response ~7 days, peak around 14 days.

Secondary response much more rapid and far stronger. (Higher affinity ABs)

Question 5

Whats an adjuvent in vaccines?

Answer 5

Something added to enhance the immune response and signal that there is danger.

Question 6

What are some examples of successful immunisation campaigns?

Answer 6

Measles Mumps Rubella Polio Diphtheria Pertussis

Question 7

What is the common mechanisms of successful vaccinations?

Answer 7

Induction of high affinity neutralising antibodies
Rapidly bind to pathogen
Prevent attachment/entry into host cells

Question 8

What are the characteristics of a good vaccine?

Answer 8

Efficacy
Safety
Pathogen

Question 9

What characteristics make a vaccine have good efficacy?

Answer 9

• T cell dependent response (important for polysaccharide vaccines, as under 2 cant respond to these)(protein+polysc conjugation gets around this)
• Elimination (of pathogen, so cant carry it asymptomatically)
• Protection
• Memory
• High uptake (80 – 90%)

Question 10

What makes a vaccine safe?

Answer 10

• No risk of causing disease

* Side effects no worse than natural disease symptoms

Question 11

What makes a good pathogen for a vaccine?

Answer 11

• Acute rather than chronic disease
• Induces immunity upon natural exposure
• Undergoes little antigen variation
• Does not attack immune system cells
• No animal or environmental reservoir

Question 12

What are some features that make a vaccine effective, in terms of immune system regulation?

Answer 12

• Induces neutralizing antibodies
  
  • some pathogens i.e polio infect cells that can to replaced i.e neurons therefore critical to neutralise them
• Induces Protective T cells
• IC pathogens must be dealt with by cellular mechanims

Question 13

What are some practical considerations for vaccinations?

Answer 13

• low cost
• biologically stable
• ease of administration
• Few side effects

Question 14

Whats a challenge to vaccine uptake?

Answer 14

• ~75% uptake required for herd immunity
• No personal experience of once common diseases
• Popular media emphasise vaccine risks – lose sight of the enormous benefit
-1970’s: UK, Pertussis Vaccine
-1990’s: UK, Measles Vaccine

Question 15

Whats defines a successful vaccine?

Answer 15

Successful vaccine:

stimulates an effective immune response to target antigens without itself causing disease

Question 16

What does attenuating a vaccine mean?

Answer 16

• Growth in vitro can lead to loss of virulence (ability to replicate in humans)
• This definition Extended to use of killed/inactivated organisms

Question 17

What are some examples of attenuated pathogens used in vaccines?

Answer 17

• Examples:
– Live: smallpox, BCG, measles, mumps, rubella, oral polio
– Inactivated: typhoid, plague, cholera, Hep A, polio
– Subunit: anthrax, tetanus

Question 18

What are the most common toxoid vaccines (vaccines that use toxins)?

Answer 18

• Combined diphtheria/tetanus/pertussis vaccine (DTaP)

Question 19

What are subunit vaccines?

Answer 19

• Subunit vaccine
– Chemically inactivated toxins or toxoids from each bacterium
– Retain antigenic properties
– Vaccination stimulates neutralising antibodies to the toxins

Question 20

What are some new developments in vaccines?

Answer 20

• Better defined adjuvants
• Better strategies for identifying antigens
• Improved manufacturing processes
• Vaccine delivery vehicles
• Alternative delivery routes (mucosal vs intramuscular)
• Response to emerging pathogens

Question 21

What is the modern approach to vaccine development?

Answer 21

Recombinant technology

> Obviates need to work with pathogenic material

Question 22

What is an aim of new vaccine development?

Answer 22

• Use conserved epitopes that are associated with protective immunity
• Downside with using more complicated epitopes is that there is the potential for autoimmune diseases or less specific immune response than wanted.

Question 23

What are the Limitations of purified recombinant antigen vaccines?

Answer 23

Highly purified/defined vaccines do not always fully recapitulate the immune response to a natural infection
e.g. Pertussis vaccine: rapid waning of protective immunity; fails to prevent colonisation and transmission

Question 24

What are some better adjuvents?

Answer 24

TLR3 activating adjuvents (flu vaccine)

TLR5 activated by flagellin

Modified bacterial toxins: e.g. CT, LT

Question 25

What is reverse vaccinology?

Answer 25

Genome sequence of target pathogen

In silico prediction of vaccine candidate antigens (make sure theyre not similar to human proteins) Refine the parameters until a very specific protein can be sued for vaccination that produces an immune response highly specific to that pathogen

Question 26

What is currently being done for flu vaccines?

Answer 26

Synthetic production of vaccines and culture use.

Use of non-pathogenic bacteria to deliver vaccine antigens