Vaccination Flashcards

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1
Q

Features of effective vaccines (x6)

A

1) Safe -must not itself cause illness or death
2) Protective -must protect against illness resulting from exposure to live pathogens
3) Gives sustained protection -protection against illness must last for several years
4) Induces neutralizing antibody -some pathogens (ie polio) infect cells that cannot be replaced (ie neurons). Neutralixing antibody is essential to prevent infection of such cells
5) Induces protective T-cells -some pathogens, particularly intracellular, are more effectively dealt with by cell-mediated responses
6) Practical considerations -low cost per dose, biological stability, ease of administration, few side-effects

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2
Q

Challenges to Vaccine Development (x3)

A

a) pathogens that provoke weak immune responses
b) pathogens that have large numbers of strains
c) pathogens that evade the immune response and elicit chronic illness

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3
Q

Precautions

  • Age and timing of immunizations
  • Hazards
A
Age and timing
   -Newborn: immaturity of immune system
   -Children
   -Elderly
Hazards
   -Immunocompromised patients:
      -AIDS, immunosuppressive  therapy
      -pregnancy: live virus may cross placenta
   -Hypersensitivity
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4
Q

Types of Vaccines

A

1) Live attenuated organisms
2) Killed or non-viable organisms
a) Whole protein organisms
b) Part of organism
- toxoids
- subunit vaccines
- capsular polysaccharides
- conjugate vaccines
3) Recombinant ENA
4) DNA vaccines

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5
Q

Live-attenuated vaccines

A

live organisms that are no longer able to cause disease, can be used to stimulate immunity

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6
Q

Attenuated viruses

A
Yellow fever
Chickenpox
Polio (sabin)
Measles, Mumps, Rubella
   -MMR given at 15 mo and 4-6 yr
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7
Q

Attenuated bacteria

A

Bacille Calmette-Guerin (BCG) -bovine strain of M.tuberculosis
Salmonella typhi

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8
Q

Attenuation

A

1) live organisms mutated to reduce pathogenicity
- can occur naturally as variants can arise that are less pathogenic (ie one of the oral sabin strains for polio -sabin 2)
2) attenuation can be done by growing viruses on non-human cell lines or animals
- selects for variant viruses that grow better in non-human cells and are less fit to grow in humans (ie cold adapted influenza virus -won’t grow at 37C)
3) attenuation can be done by genetic engineering
- (ie Salmonella typhi (typhoid fever) made mutagenesis of enzyme necessary for LPS synthesis)

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9
Q

Advantages of Attenuated vaccines

A

strong immune responses, can mimic the natural disease process and therefore immunity is generated to target the infectious process -this includes route of infection

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10
Q

Disadvantages of Attenuated vaccines

A

can cause problems in immunocompromised individuals, chance of reversion to pathogenic form

*Sabin oral polio vaccine contains 3 diff. live-attenuated viruses (trivalent). 3 people/million can develop polio from this, a result of strain 3 where reversion of one nucleotide results in virulence. Current solution, give killed vaccine first immunization with the live viruses subsequently

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11
Q

Killed or non-viable (inactivated) vaccines

-Whole organisms

A

Whole organisms:

1) Viruses (Salk polio virus, influenza, rabies)
- chemically treated or heated or irradiated so that they are no longer able to replicate
- trivalent influenza virus (grown in eggs) and inactivated using formalin
2) Bacteria (Bordetella pertussis or Vibrio cholera)
- killed organism extract

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12
Q

Disadvantage of inactivated whole organism

A

More side effects related to immune pathology or specific antigens that mediate the disease caused by the microbe

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13
Q

Killed or non-viable (inactivated) vaccines

-Part of Organism

A

Part of organism:

1) Target toxins using toxins inactivated with formalin (toxoids)
- e.g. diptheria toxin, tetanus toxin
- single vaccine is DTP with diptheria toxoid, tetanus toxoid, killed pertussis

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14
Q

Killed or non-viable (inactivated) vaccines

  • Subunit vaccines
    - >Capsular polysaccharides
    - >Conjugate vaccines
A

Subunit Vaccines

  • Hepatitis B virus (HbsAg) -purified from blood from patients or recombinant protein
  • Encapsulated bacteria -antibody responses against CAPSULAR POLYSACCHARIDES are protective (ie S.pneumoniae, N. meningitis, H.influenza)
  • > Capsular polysaccharides can provoke T-independent B cell responses, but not very immunogenic in infants or in elderly
  • > Conjugate vaccines -conjugate toxoid (tetanus, diptheria) to polysaccharide converts to T dependent antigen
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15
Q

Conjugate Vaccines
-how do they work?

(slide 15)

A

1) B cell binds bacterial polysaccharide epitope linked to tetanus toxoid protein
2) Antigen is internalized and processed
3) Peptides from protein component are presented to the T cell
4) Activated B cell produces antibody against polysaccharide antigen on the surface of the bacterium
5) Activated B cell will proliferate and become either a polysaccharide specific memory or plasma cell

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16
Q

Recombinant DNA Vaccines

A

Insert genes for specific antigens into non-virulent viral or bacterial organisms

1) Salmonella vectors
- encoding antigenic genes for listeria, anthrax, plague
- administered orally
2) Vaccinia vectors
- no longer used to protect against smallpox
- avirulent carrier of heterologous antigens
3) Adenoviral vectors
- used for HIV vaccine development
- cancer immunotherapy

17
Q

DNA Vaccines

A

Naked DNA plasmid injected into muscle induces flu-specific CD8, CD4, and Ab responses
-presumably the plasmid DNA is expressed by some of the muscle tissue

18
Q

Adjuvants

A
  • Killed/non-viable vaccines are not very immmunogenic themselves and requires an adjuvant to enhance immunity
  • Vaccination can be enhanced by the addition of substances (adjuvants) that induce inflammation by antigen-independent mechanisms
    1) Freund’s complete adjuvant: emulsion of killed mycobacteria and mineral oil
    2) Alum (aluminum hydroxide): only approved adjuvant in US (MF59 in Europe)
    • tends to promote Th2 type responses, not Th1
19
Q

A prerequisite to a good ____________________ is a state of _____________ due to _____________activation and recruitment of __________________.

A

adaptive immune response; inflammation; macrophage, inflammatory cells

20
Q

Improvements in vaccine development and design

A

1) Understand disease pathogenesis better to identify targets
-using recombinant DNA tech. to produce purified vaccine proteins (HBV-HBsAg) or reduce virulence (Salmonella)
2) Need to understand how the immune system best protects from an infectious disease
-Th1 vs Th2 -addition of IL-12 can promote Th1
-route of immunization -site of infection
3) Improve adjuvants
-ISCOMS (Immune Stimulatory Complexes)
->lipid micelles, carrying class I restricted peptides or polypeptides, fuse with cell membrane and deliver them to cytoplasm
-Cytokines as molecular adjuvants
(eg GM-CSF, IL-2)