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204-theme 1 > T1 l7:vaccines > Flashcards

T1 l7:vaccines Flashcards

1
Q

what is immunisation

A

Immunisation is an artificial process by which an individual is rendered immune

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2
Q

what are the different categories of the immune system

A
  • Passive immunisation – no immune response in recipient

- Active immunisation (vaccination) – recipient develops a protective adaptive immune response

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3
Q

expand on passive immunisation

A

Immunity conferred without an active host response on behalf of recipient

Passive vaccines are preparations of antibodies taken from hyper-immune donors, either human or animal
Examples:

Immunoglobulin replacement in antibody deficiency

VZV prophylaxis eg during exposure during pregnancy

Anti-toxin therapies eg snake anti-serum

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4
Q

expand on active immunisation

A

Immunity conferred in recipient following the generation of an adaptive immune response

General principle is to stimulate an adaptive immune response without causing clinically-apparent infection

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5
Q

what are the 2 general principles of active immunity

A

1- Vaccination of sufficient numbers impacts the transmission dynamic so that even unimmunised individuals are at low risk – called herd immunity
As vaccines are given to healthy individuals, the risk-to-benefit ratio requires that vaccines meet high safety standards

2- Most vaccines work by generating a long-lasting, high-affinity IgG antibody response
These antibodies are sufficient to prevent primary infection
A strong CD4 T cell response is a pre-requisite for this
The most effective vaccines are for diseases where natural exposure results in protective immunity

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6
Q

what forms a vaccine

A

Antigen-
To stimulate an antigen-specific T and B cell response

Adjuvants-
Immune potentiators to increase the immunogenicity of the vaccine

‘Excipients’-
Various diluents and additives required for vaccine integrity

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7
Q

how do you classify active vaccines based on the antigen

A

can be subunit- toxoids, capsular polysaccharide, recombinant subunit , conjugated polysaccharide

it can also be a derivation of the whole organism:

  • Live-attenuated
  • inactivated (killed)
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8
Q

how do you classify active vaccines based on the antigen

A

can be subunit- toxoids, capsular polysaccharide, recombinant subunit , conjugated polysaccharide

it can also be a derivation of the whole organism:

  • Live-attenuated
  • inactivated (killed)
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9
Q

what are the examples of live-attenuated vaccines

A 
Measles
Mumps
Rubella
Polio (Sabin)
BCG 
Cholera
Zoster
VZV (not routinely used for primary prevention in UK at present)
Live influenza (not routinely used in UK at present)
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10
Q

evaluate the use of live vaccines

A

Advantages:
Replication within host, therefore produces highly effective and durable responses

In case of viral vaccine, intracellular infection leads to good CD8 response

Repeated boosting not required

In some diseases, may get secondary protection of unvaccinated individuals, who are infected with the live-attenuated vaccine strain eg polio

Disadvantages:
Storage problems, short shelf-life

May revert to wild type

Eg vaccine associated poliomyelitis: around 1 in 750 000
recipients

Immunocompromised recipients may develop clinical disease

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11
Q

describe the varicella-zoster vaccine

A

Primary infection = chickenpox

Cellular and humoral immunity provide lifelong protection, but viruses establishes permanent infection of sensory ganglia

Viral reactivation=zoster

Particularly elderly, fairly debilitating and may cause long-term neuropathic pain

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12
Q

how does the VZV vaccine work

A

Live-attenuated VZV, works by induction of anti-VZV antibodies
95% effective at preventing chickenpox
Attenuated virus does establish infection of sensory ganglia, but subsequent zoster is probably rare

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13
Q

what is the zoster vaccination

A

Similar VZV preparation, but much higher dose

Aims to boost memory T cell responses to VZV

In over 60s, 50% reduction in zoster incidence after vaccination compared to controls; reduced severity and complications amongst vaccinated cases

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14
Q

describe poliomyeitis

A

Enterovirus establishes infection in oropharynx and GI tract (alimentary phase)

Spreads to peyers patches then disseminated via lymphatics

Haematogenous spread (viremia phase)

1% of patients develop neurological phase: replication in motor neurones in spinal cord, brainstem and motor cortex, leading to denervation and flaccid paralysis

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15
Q

Salk vs Sabin Polio vaccine

A

Sabin oral polio vaccine (OPV) = live-attenuated

  • Viable virus can be recovered from stool after immunisation
  • Highly effective, and also establishes some protection in non-immunised population
  • 1 in 750 000 vaccine-associated paralytic polio

Salk injected polio vaccine (IPV) = inactivated

-Effective, but herd immunity inferior

OPV better suited to endemic areas, where benefits of higher efficacy outweigh risks of vaccine-associated paralysis. UK switched to IPV in 2004

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16
Q

describe infection of Tb

A

During primary infection, MTB establishes infection within phago-lysosomes of macrophages. Macrophages present TB antigen to MTB-specific CD4 T cells, which secrete IFN-g – this activates macrophages to encase TB in granuloma.

May be visible as a calcified lesion on plain CXR (Ghon focus)

Most TB thought to be re-activation of this primary infection

17
Q

describe the vaccination for Tb

A

Only licensed product is BCG (bacille Calmette-Guerin)

Produced by repeat passage of a non-tuberculus mycobacterium: Mycobacterium bovis

Aims to increase Th1 (IFN-g) cell responses to M bovis, thereby conferring protection against MTB

Given by intradermal injection

80% effective in preventing disseminated TB/ TB meningitis in children; little or no effect on pulmonary TB

18
Q

is the TB vaccine alive?

A

Entire organism used, but physical or chemical methods used to destroy viability (eg formaldehyde)

Stimulates B cells, and taken up by antigen-presenting cells to stimulate antigen-specific CD4 T cells

Probably elicit minimal CD8 response, as the vaccine cannot undergo intracellular replication

Responses less robust compared to live-attenuated vaccines

Examples

  • Hepatitis A
  • Influenza (standard vaccine – live-attenuated also available but not routinely used)
19
Q

evaluate ‘killed’ vaccines

A

advantage:
No potential for reversion
Safe for immunocompromised
Stable in storage

disadvantage:
Mainly CD4/ antibody response
Responses less durable then live vaccines
Generally boosters required
Higher uptake generally required to achieve herd immunity

20
Q

Difficulties of influenza vaccination

A

Target antigens prone to mutation (antigenic drift) causing seasonal variation – therefore vaccine produced annually based on predictions

CDC provide candidate virus strains to manufacturer; injected into fertilised hens eggs and virus then harvested (inactivated for standard vaccine)

More major changes (antigenic shift) occur when viral strains recombine – eg with animal strain, causing pandemic influenza

21
Q

describe subunit vaccines

A

Uses only a critical part of the organism

Components may be:

  • purified from the organism or
  • generated by recombinant techniques

-Protection depends on eliciting CD4 and antibody responses

22
Q

Subunit vaccines: toxoids

A

Many examples relate to toxin-producing bacteria:

  • Corynebacterium diphtheriae
  • Clostridium tetani
  • Bordatella pertussis

Toxins are chemically detoxified to ‘toxoids’

Retain immunogenicity

Work by stimulating antibody response; antibodies then neutralise the toxin

23
Q

describe tetanus

A

Pre-formed high-affinity IgG antibodies can neutralise the
toxin molecules in the circulation; the immune complexes
are then removed via the spleen

Anti-toxin can also be given in established cases (passive immunisation)

24
Q

describe subunit vaccines: polysaccharide capsules

A

Thick polysaccharide coats of Streptococcus pneumoniae and Neisseria meningitidis make them resistant to phagocytosis

Vaccines for these organisms formed of purified polysaccharide coats

Vaccines formed of purified polysaccharide coats; aim to induce IgG
antibodies that improve opsonisation

Suboptimal as polysaccharides are weakly immunogenic:

  • No protein/ peptide, so no T cell response
  • Stimulate a small population of T-independent B cells

Latest vaccines utilise vaccine conjugation to boost responses: protein carrier attached to polysaccharide antigen

25
Q

what is vaccine conjugation

A

1-Naive B cell expressing surface IgM recognises polysaccharide antigen. Antigen is internalised together with the protein conjugate

2- Conjugate is processed in the class II pathway. Naive B cell presents peptides from the conjugate to a helper T cell with the correct receptor.

3- T cell helps the B cell to perform affinity maturation, but antibody is specific for the polysaccharide and not for the protein conjugate

26
Q

recombinant protein subunit vaccine

A

Purified to produce vaccine

  • Hepatitis B surface antigen
  • HPV vaccine
27
Q

Pros and cons of subunit vaccines

A

pros:
-Extremely safe

  • Work well where primary infection may be prevented by an antibody response
  • Works when the virus cannot easily be cultured eg HPV and Hep B

cons:

  • Development requires detailed knowledge of virology, pathogenesis and immunology
  • Specialised and expensive production
  • Weaker immune responses – boosting often needed and response rate varies
28
Q

describe novel approaches: viral vector

A

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

Altered virus used as a live-attenuated vaccine

Use restricted to animals to date

29
Q

describe novel approaches: DNA vaccines

A

Plasmid DNA that encodes vaccine antigen of interest applied; taken up by cells, transcribed and translated

Elicits host immune response

Mainly performed in mice models

Poorly immunogenic to date in human trials

204-theme 1 (15 decks)

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