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L6- Vaccines Flashcards

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1
Q

What year was Edward Jenner’s smallpox vaccine introduced?

A

1796

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2
Q

The global eradication of smallpox was announced by the WHO in what year?

A

1980

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3
Q

What is variolation?

A

The inoculation of a small amount of dried material from a smallpox pustule would cause a mild infection followed by long-lasting protection against reinfection

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4
Q

How did the smallpox vaccine come about?

A

Jenner realised that infection with a bovine analogue of smallpox, vaccinia, which caused cowpox would provide protective immunity against smallpox in humans without the risk of significant disease.

Humans are not a natural host of vaccinia, which establishes only a brief and limited subcutaneous infection but contains antigens that stimulate an immune response that is cross-reactive with smallpox antigens and thereby confers protection from human disease.

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5
Q

Vaccinia-specific T cells and antibody responses last up to ______ years after original immunisation?

A

75 years

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6
Q

How can the memory T cells sustain for so many years?

A

Does not require repeat exposure to retain memory. Memory cells may be sustained by cytokines produced in response to infection with other, unrelated pathogens

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7
Q

What is the purpose of herd immunity?

A

When a critical portion of the community is immunised against a contagious disease, most members of the community are protected against that disease because there is little opportunity for an outbreak.

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8
Q

Virus spread stops when the probability of infection drops below a critical threshold, which is virus and population specific.

What population is immune from measles?

A

93-95%

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9
Q

What is subacute sclerosing panencephalitis (sspe)?

A

A slow growing infection of the cns associated with prior measles infection

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10
Q

What is the estimated mortality rate for malaria world wide?

Annual incidence?

A

Mortality? 1,124,000

Incidence: 300-500 million people

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11
Q

What is the estimated mortality rate for tuberculosis world wide?

Incidence?

A

Mortality: 1,644,000

Incidence: 8 million

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12
Q

What is the estimated mortality rate for measles world wide?

Incidence?

A

Mortality: 745,000

Incidence: 44 million

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13
Q

What is the estimated mortality rate for diarrheal diseases worldwide?

Incidence?

A

Mortality: 2,001,000

Incidence: 4,100 million

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14
Q

What is the worldwide mortality rate for HIV/aids?

Incidence?

A

Mortality: 2,866,000

Incidence: 2 million

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15
Q

What is the worldwide mortality rate for respiratory diseases?

Incidence?

A

Mortality: 3,947,000

Incidence: 362 million

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16
Q

What are the principles of vaccination?

A
  1. Pathogens are altered so that they maintain their antigencity while losing their virulence.
  2. Vaccination induces primary antibody and cellular immune responses
  3. Memory cells proliferate rapidly in secondary immune responses induced in natural infection
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17
Q

Define active immunity?

A

Protection produced by a persons own immune system, with specificity and memory which can last decades

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18
Q

Define passive immunity?

A

Protection transferred from another person or animal (Antibody only)

This is only temporary protection as it wanes with time.

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19
Q

What is the half-life of Ab?

A

21-28 days

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20
Q

List some advantages of live attenuated vaccines over killed vaccines

A
  •   Most closely resembles wild-type pathogen; immune response best matches protective immune response
  •   Can replicate in vaccinee target cells- will induce an immune response that most closely resembles natural infection with formation of protective memory.
  •   Usually effective with one dose, and does not require boosters
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21
Q

List some disadvantages of live attenuated vaccines

A
  •   Severe reaction is possible, especially in immunocompromised individuals
  •   Attenuated virus must replicate in order for vaccine to be effective
  •   Reversion to wild-type virulent form is possible
  •   Interference form pre-existing antibody to vaccine antigen/vector in the host
  •   Vaccine antigen will be inactivated under incorrect storage conditions (especially temperature) and must be stored correctly: cold chain requirements when delivering vaccine to remote areas
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22
Q

Explain the method for deriving live attenuated vaccines.

A
  1. The pathogenic virus is isolated from a patient and grown in human cultured cells
  2. The cultured virus is used to infect MONKEY cells
  3. The virus acquired many mutations that allow it to grow well in monkey cells
  4. The virus no longer grows well in human cells (it is attenuated) and can be used as a vaccine.
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23
Q

Why are inactivated or “killed” vaccines are not as effective with creating an immune response?

A

They are unable to replicate or produce proteins in the cytosine so peptides from the viral antigen cannot be presented by MHC class I molecules and thus cytotoxic CD8 T cells are not generated by these vaccines.

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24
Q

What is Yellow fever caused by?

A

Infection with arthropod-borne flavivirus Yellow Fever virus,

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25
How is Yellow Fever transmitted?
By Aedes mosquitoes
26
Where does Yellow Fever occur?
Primarily in sub-Saharan Africa and South America.
27
Describe disease spectrum of Yellow Fever vaccine
*   Disease spectrum ranges from mild acute viral illness (self-limiting) to total organ failure *   More serious illness presents with: - Malaise - Fever - Chills - Nausea - Headache - Vomiting - Abdominal pain - Renal failure - Multi organ failure - Death
28
What is the term to describe multi-organ failure and death due to Yellow Fever Vaccine?
Yellow Fever vaccine-associated viscerotropic disease (YEL-AVD)
29
What is the fatality rate of YEL-AVD?
>20%
30
How common is YEL-AVD?
>200,000 cases/year including fatal cases in Western travellers to endemic countries
31
What did Max Theiler work on that involved YFV (West African Asibi Strain) Yellow Fever?
Passaged YFV through mice and challenged rhesus monkeys After >100 subcultures, derived stain 17-D which was PROTECTIVE in that it induced neutralising antibodies YFV-17D ended Yellow Fever as a major disease
32
What year did Max Theiler receive a Nobel Prize for YFV-17D vaccine?
1951
33
How is a virus inactivated (killed) to use as a vaccine?
By heat or chemicals but allows them to remain antigenic
34
Provide an example of inactivated vaccines
``` Pathogen components Protein based -toxoid -subunit E.g. Tetanus toxoid ``` polysaccharide based -pure -conjugate E.g. Meningococcal polysaccharide Whole organisms -viruses -bacteria E.g. Cholera
35
Provide an example of a bacterium that causes disease but do not produce toxins
Neisseria meningitidis (meninggococcus) Streptococcus pneumoniae (pneumococcus) Haemophilus influenzae type B
36
What disease does Haemophilus influenzae type B cause?
- Septicaemia - Meningitis - Otitis media - Pneumonia
37
What makes up a polysaccharide made up of?
A piece of the bacterial polysaccharide capsule as the immunogen
38
Why are polysaccharide vaccines not suitable for children under 2 years of age and how can you overcome this?
Most of the polysaccharides are thymus-independent (TI)-2 antigens which induce an inadequate immune response in neonates and infants as their immune system is not matured. The mechanisms that are thought to play a role in the unresponsiveness of this age group to TI-2 stimuli will be discussed. The lack of immune response may be overcome by conjugating the polysaccharides to a carrier protein. This transforms bacterial polysaccharides from a TI-2 antigen into a thymus-dependent (TD) antigen, thereby inducing an immune response and immunological memory in neonates and infants. Such conjugated vaccines have been shown to be effective against the most common causes of invasive disease caused by encapsulated bacteria in neonates and children.
39
Why are polysaccharide vaccines not suitable for children under 2 years of age and how can you overcome this?
Most of the polysaccharides are thymus-independent (TI)-2 antigens which induce an inadequate immune response in neonates and infants as their immune system is not matured. The mechanisms that are thought to play a role in the unresponsiveness of this age group to TI-2 stimuli. The lack of immune response may be overcome by conjugating the polysaccharides to a carrier protein. This transforms bacterial polysaccharides from a TI-2 antigen into a thymus-dependent (TD) antigen, thereby inducing an immune response and immunological memory in neonates and infants. Such conjugated vaccines have been shown to be effective against the most common causes of invasive disease caused by encapsulated bacteria in neonates and children.
40
What is a conjugate vaccine?
Protein antigen attached to polysaccharide antigen
41
Haemophilus influenza type B is a conjugate with tetanus toxoid proteins. Explain how the B cell recognises the antigen
Once internalised and degraded the whole conjugate and then displays toxoid-derived peptides on surface MHC class II molecules. Helper T cells generate in response to earlier vaccination against the toxoid so that B cells produce anti-polysaccharide antibody
42
In the US: Sabin attenuated vaccine-associated polio was responsible for how many viral infections?
1 in 400,000
43
What response did we see in Scandinavia with the Salk dead vaccine?
No gut immunity and cannot wipe out wt virus
44
What are some advantages of subunit vaccines for active immunisation?
*   Prepared from compounds of viral proteins. May self aggregate to produce virus-like particles *   Recombinant DNA technology *   No viral genomes or infectious virus
45
What are some disadvantages of subunit vaccines for active immunisation?
*   Expensive *   Injected *   poor antigenicity
46
Wha do subunit vaccines active immunisation have in common with inactivated vaccines?
*   Viral proteins don’t replicate or infect *   Don’t cause inflammation *   Require adjuvants to induce / mimic inflammatory effects of infection
47
Patients with Hapatitis B secrete what type of surface antigen?
HBsAg Comprised of 3 glycoproteins encoded by the same gene.
48
How did the vaccine for Hep B come about?
In 1982, a recombinant form was produced in yeast that formed particulate structure. This for, of the vaccine became available in 1986.
49
What is an advantage of using non infectious virus-like particles ?
They induce Hugh titres of virus-neutralising antibodies even I the absence of an adjuvant.
50
What is a successful vaccine using non-infectious virus like particles?
Vaccine for Ha]uman Papilloma virus (HPV) type 16.18 (cervical cancer), 6 and 11 (genital warts) Vaccine: Gardasil
51
What makes up the influenza A vaccine?
It is a subunit vaccine that includes HA and NA proteins HA: Hemagglutinin NA: Neuraminidase
52
What are some safety problems with active immunisation?
*  Mild toxicity most common *   Risk of anaphylactic shock *   Residual virulence from attenuated viruses *   People believe allegations that certain vaccines cause autism, diabetes and asthma
53
What is passive immunisation made of?
•  Administration of antiserum containing performed antibodies
54
What is an advantage of passive immunisation?
Provides immediate protection against recent infection or ongoing disease.
55
What are some limitations of Antisera a passive immunisation?
*   Contain antibodies against antigens *   Can trigger hypersensitivity reactions called serum sickness *   Viral pathogens May contaminate antisera *   Antibodies of antisera are degraded relatively quickly *   Temporary protection *   Transfer of antibody produced by one human or animal to another *   Transplacental most important souse in infancy
56
How is rabies transmitted?
Rabies is a viral zoonotic disease spread to humans via a bite from an infected animal (mostly dogs and bats)
57
How does rabies affect the human body?
Virus travels along nerves from bit site to CNS. Most people with symptomatic rabies do not survive.
58
How can you prevent disease once bitten by a rabid dog?
There is a delay in infection and arrival in CNS means post-exposure prophylaxis can prevent disease
59
What vaccine is provided for rabies?
Inactivated vaccines (killed virus) or rabies immunoglobulin are offered, depending on exposure and degree of risk
60
What is immunogenicity?
Immunogenicity is the property of inducing an immune response.
61
Various properties of an antigen with influence the strength of immune response initiated by immunogenicity, what are some examples?
*   Large protein size *   Immediate dose *   Route *   Particulate or denatured form *   Multiple differences from self protein *   Slow release adjuvants / bacterial adjuvant *   Effective interaction with host MHC
62
What are 3 ways you can enhance immunogenicity by targeting it to an APC?
1. Prevent proteolysis of the antigen on its way to APC’s. This is an important reason why so many vaccines are given by infection instead of oral route which exposes vaccine to digestion in the gut. 2. Target the antigen selectivity to APC 3. Devise methods of engineering the selective uptake of the vaccine into antigen-processing pathways within the cell.
63
What is an adjuvant?
An adjuvant is a substance added to a vaccine to increase the body’s immune response to the vaccine
64
How do adjuvants work?
*   Acting an an antigen depot, releasing it slowly | *   Inducing an inflammatory response that enhances the host immune response to the vaccine antigen.
65
What are some examples of licensed adjuvants?
*   Alum (aluminium hydroxide or phosphate) in HBV *   Monophosphoryl lipid A (isolated from surface of bacteria; TLR-4 ligand) in HPV vaccine *   MF59 (squalene oil-in-water emulsion; antigen depot) for influenza vaccine
66
What are some features of an effective vaccine?
*   Safe (must not itself cause illness or death) *   Protective against illness resulting from exposure to live pathogen *   Gives sustained protection to last several years *   Induced neutralising antibody *   Induces protective T cells *   Low cost per dose *   Biological stability *   Ease of administration *   Few side effects

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