Vaccines & Vaccine development Flashcards

1
Q

What is immunisation?

A

artificial process by which an individual is rendered immune

- passive or active

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2
Q

Describe passive immunity

A
  • no immune response in recipient
  • preparations of antibodys from hyperimmune donors (animal/human)
  • e.g anti-snake venom, VZV prophylaxis in pregnancy
  • immunity acquired is TEMPORARY
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3
Q

Describe active immunity

Why is this important in public health and prevention of disease?

A
  • aka VACCINATIONS
  • recipient develops a protective adaptive immune response without causing clinically apparent infection

Cheap and effective way of decreasing morbidity and increasing survival

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4
Q

State 5 conditions required for a vaccination to be most effective

A
  • administered to targeted cohorts in ADVANCE
  • herd immunity (>90%)
  • meet high safety standards
  • generate long lasting high affinity IgG antibody response (enough to prevent primary infection)
  • requires strongCD4 T cell response
  • natural exposure results in protective immunity
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5
Q

Briefly describe the use of passive immunity in VZV prophylaxis in pregnancy

A
  • “Chickenpox” infection in pregnancy causes fetal complications
  • VZIG (prophylaxis) is indicated if VZV IgG is negative in maternal blood, otherwise reassure
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6
Q

State 3 diseases for which vaccinations have poor efficacy

Suggest why

A

Common cold, HIV, malaria

Immune system cannot eliminate infection or generate long lasting protective immunity

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7
Q

What is inside a vaccine?

A

Antigen
Adjuvant
Excipients
* Active vaccines can be made from whole organisms (live attenuated or inactivated) or subunits

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8
Q

How are live attenuated vaccines prepared

Give 5 examples of vaccinations prepared in this way

A

Prolonged culture ex vivo in non-physiological conditions which selects variants adapted to live in culture
- These are able to live in vivo but no longer cause disease

MMR, Polio, BCG, Cholera, Zoster, VZV, Live influenza

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9
Q

State 4 advantages of using live attenuated vaccines

A
  • replication in host produces highly effective and durable responses
  • in viral cases, intracellular infection leads to good CD8 response
  • repeated boosting not required
  • may get secondary protection of unvaccinated people who are infected (e.g. polio)
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10
Q

State 3 disadvantages of using live attenuated vaccines

A
  • storage problems due to short half life
  • may revert to wild type e.g. in vaccine associated poliomyelitis
  • immunocompromised recipient may develop disease
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11
Q

Describe the consequences of primary infection with VZV

What happens in reactivation?

How does a vaccine work in this case?

A

Primary infection (chickenpox) provides lifelong immunity but virus establishes permanent infection of sensory ganglia

Reactivation = zoster. Particularly in elderly patients. It is debilitating and causes long term neuropathic pain

Vaccine induces anti-VZV anitbodies (95% effective against chickenpox) but not used in UK.
- 3-5% develop post vaccination mild varicella infection

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12
Q

How has the disease shift of VZV impacted the tolerance of the virus in the older population?

A
  • VZV benign childhood infection is less tolerated if contracted by an unvaccinated adult
  • Increased development of zoster (less immune boosting in adults)
  • The incidence of zoster increases with age
  • Vaccination is similar to VZV but higher dose and its aim is to boost memory T cell response to VZV. The result is that there is a 50% decreases in incidence and less severe and complicated cases
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13
Q

Describe how the infection resulting in poliomyelitis occurs

A
  • enterovirus establishes infection in oropharynx and GIT (alimentary phase)
  • spreads to peyers patches and disseminates into lymphatics
  • haematogenous spead (viremia phase)
  • 1% develop neurological phase: denervation and flaccid paralysis due to replication in motor neurons in spinal cord, brainstem and motor cortex
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14
Q

There are two types of vaccines against poliomyelitis.

Describe the production, efficacy and side effects of the SABIN ORAL POLIO VACCINE (OPV)

A

LIVE ATTENUATED VACCINE

  • viable virus obtained from stool post-immunisation
  • highly effective and also establishes protection in non-immunised population
  • better suited to endemic areas where benefits of high efficacy outweigh risks
  • side effects: 1/750000 develop vaccine associated paralytic polio
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15
Q

There are two types of vaccines against poliomyelitis.

Describe the efficacy of the SALK INJECTED POLIO VACCIN (IPV)

A

INACTIVATED VACCINE

  • effective although herd immunity inferior to OPV
  • switched in 2004
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16
Q

What happens in primary infection of mycobacterium tuberculosis?

How does it appear on XR?

A
  • MTB establishes infection in phago-lysosomes of macrophages. Macrophages present TB antigen to specific CD4 T cell which secretes IFN-g which activates macrophages to encase TB in granuloma
  • Granuloma appears as calcified lesion
17
Q

Describe the use, aims, administeration and efficacy of the tuberculosis vaccine

A
  • Licensed vaccine is BCG produced by repeat passage of a non-MTB e.g. mycobacterium bovis
  • Aims: increase Th1 (IFN-g) cell responses to M.bovis –> confer immunity to MTB
  • Administered via intradermal injection
  • 80% effective in preventing disseminated TB/ TB meningitis in kids. Little/no effect on pulmonary TB
18
Q

How are killed (inactivated) vaccines prepared?
How do they work?

Give 2 examples of vaccinations prepared in this way

A
  • Entire organism used but physical/chemical methods used to destroy viability (e.g. formaldehyde)
  • Stimulate B cells, taken up by APCs to stimulate CD4 T cells. They elicit minimal CD8 response as vaccine cannot undergo intracellular replication.

e.g. Hep A, Influenza

19
Q

State 3 advantages and disadvantages of using killed (inactivated) vaccines

A

ADVATANGES

  • No potential for reversal
  • Safe for immunocompromised
  • Stable in storage

DISADVANTAGES

  • mainly CD4/AB response
  • response less durable that live (booster required)
  • higher uptake needed for herd immunity
20
Q

How does the influenza virus work?

A

Protective AB responses largely directed against haemagglutinin and neuramidase and work by blocking entry to cells, blocking release of new virons from infected cells and promoting ADCC (antibody-dependent cellular cytotoxicity)

21
Q

Why is an influenza vaccine not all that effective?

A
  • Target antigens prone to mutations (autogenic drift) which is responsible for seasonal variation
  • Major changes occur when viral strains recombine (e.g. with animal strain) –> pandemic influenza
22
Q

How are subunit vaccines prepared?
How do they work?

Give 2 examples of vaccinations prepared in this way

A
  • only use critical part of organism which is then purifies from organism or generated by recombinant techniques
  • protection depends on eliciting CD4 and AB responses

e.g. toxoids, tetanus vaccine

23
Q

What are toxoids?

How do they produce immunity?

A
  • Chemically detoxified toxins
  • e.g. toxin producing bacteria: C,diphtheriae, C.tetani, B.pertussis
  • retain immunogenicity
  • work by stimulating AB response; antibodies neutralise toxin
24
Q

How does the tetanus vaccine work?

A
  • preformed high affinity IgG neutralise toxin in circulation; immune complexes then remove via spleen
  • anti-toxin can also be given in extablished cases (passive immunity
25
Q

What are polysaccharide capsules?
Where are they found? How can they be used therapeutically?

Disadvantages of their use?

A
  • Thich PS coat bacteria such as S. pneumonaie, N.meningitidis which makes them resistant to phagocytosis
  • Vaccines against these bacteria are formed from PS coat and their aim is to induce IgG antibody that improves opsonisation
  • Suboptimal as PS weakly immunogenic. If no peptide –> no T cell response and only stimulates small population of T-independent B cells
26
Q

How is the efficacy of vaccines made from polysaccharide coats boosted?

Explain the process.

A

Vaccine conjugation boosts immune response by attaching protein carrier to PS antigen

  • naive b cell expressing surface IgM recognises polysaccharide antigen. Antigen is internalised together with protein conjugate
  • conjugate is processed in the class 2 pathway. Naive B cell peptides from conjugate to a Th cell with correct receptor
  • T cell helps the b cell to perform affinity maturation but antibody is specific for polysaccharide and not the protein conjugate.
27
Q

What must be considered when using/making recombinant protein subunit vaccines?

Eg of vaccines made in this way

A
  • need to know key immunogenic proteins required
  • proteins expressed in lower organisms
  • purified to produce vaccine
  • e.g. Hep B (uses surface antigen), HPV
  • increasingly in use
28
Q

Why is HPV vaccination important?

Why was its development difficult?

A
  • subtypes 16 and 18 cause cervical carcinoma
  • vaccine development difficult due to HPV difficulty culturing
  • subunits vaccines are ‘empty virus particles’ that prevent primary infection (Quadravalent vaccine covers additional HPV strains)
29
Q

Give three advantages and disadvantages of recombinant protein subunit vaccines

A

ADVANTAGES

  • extremely safe
  • work well where primary infection may be prevented by AB response
  • works when virus cannot easily be cultured e.g. HPV, Hep B

DISADVANTAGES

  • development requires detailed knowledge of virology, pathogenesis and immunology
  • specialised and expensive production
  • weaker immune responses- boosting often needed and varied response rates
30
Q

What are adjuvants?

Examples?
How do they work?

A

Immune potentiators to increase the immunogenicity of the vaccine

  • boost immune response to antigen
  • widely used despite lack of understanding of MOA
  • examples: alum, lipopolysaccharides
  • bind to PRRs on APCs which enhance co-stimulation and cytokine secretion, which ensures robust T/B cell response
  • novel aduvants: TLR ligands e..g CPG repeats
31
Q

How do novel DNA vaccines work?

A

plasmid DNA encodes vaccine antigen applied, taken up by cells, transcribed and translated –> elicits host immune response

  • mainly performed in mice, poorly immunogenic in humans
32
Q

Novel vaccines are using viral vectors. How does this work?

A

Benign virus that can be easily grown in culture engineered to carry genes encoding immunogenic antigens
Used in live attenuated vaccine

Use restricted to animals to date