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2. HDS Pulmonary > Antimicrobial Vaccines > Flashcards

Antimicrobial Vaccines Flashcards

1
Q

Immunization Goals

A
  1. Prevent infection and/or reduce severity of disease in a given individual
  2. Reduce transmission and if possible eradicate an infectious disease at the population level
    • Herd immunity ⇒ possible if vaccine coverage high enough
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2
Q

Protective Responses

A
  • ⊗ colonization or invasion
  • ⊗ growth and/or dissemination of microbes
  • Promote lysis and/or phagocytosis
  • Neutralize toxins
  • Counter immune evasion strategies
  • Facilitate pathogen recognition by immune system
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3
Q

Passive Immunization

Definition

A

Transfer of human (or equine) Ig w/ high concentration of Ab for specific pathogen or toxin to non-immune individuals.

Ex. passive transfer of IgG from mother to fetus

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4
Q

Therapeutic

Passive Immunization

A
  • Prevent disease in non-immune pts when high risk but not enough time for active immunization
    • Ex. needle stick w/ HBV blood
  • Reduce sx of ongoing disease
    • Ex. tetanus d/t would infection
  • Protect immunosuppressed or immunodeficient individuals
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5
Q

Passive Immunization

Pros and Cons

A
  • Pro ⇒ protection is immediate
  • Cons
    • Limited duration
    • No memory
    • Risk for subsequent infection w/ same pathogen
      • Active immunization needed if available
    • Potential for hypersentivitity rxn
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6
Q

Passive Immunization

Examples

A
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7
Q

Active Immunization

Overview

A

Prime the acquired immune response to viral antigens

  • By natural infection or vaccination
  • Results in immunologic memory
    • Prevent infection
    • Reduce disease/pathology
    • Limit transmission
  • More effective secondary immune response on subsequent exposure
  • Cheapest way to control infectious diseases
    • Ex. Variola virus ⇒ Smallpox
  • Toxoid vaccines protect against sx or pathology of disease
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8
Q

Active Immunization

Requirements

A

Present protective Ag in appropriate context to promote immune recognition and response.

Expansion of protective, pathogen specific immune effector and memory lymphocytes.

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9
Q

Vaccine Success

A
  • Efficacy
    • Nature and complexity of protective immune response
    • Ability to elicit appropriate responses by immunization
    • Duration of immunity
  • Safety
  • Stability
  • Cost
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10
Q

Target Populations

A
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11
Q

Vaccine Classes

A
  1. Live attenuated
    • Whole virus
    • Cross-reactive
  2. Whole killed
  3. Subunit (several types)
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12
Q

Live Attenuated

Vaccines

A

Sufficient to induce a protective response but limited replication in vivo

  • Serial passage in cell culture
    • Temperature-sensitive mutants
    • Host-range mutants
    • Ex. MMR
  • Targeted genetic modification
    • Deletion of virulence factors
    • Modify membrane proteins
    • Creation of nutritional auxotrophs
    • Ex. Salmonella typhi, Vibrio cholera
  • Often results in a very robust response
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13
Q

Antigenically Cross-reactive

Vaccines

A

Non-human pathogen that shares enough Ag to produce a cross-reactive, protective immune response

  • Live pathogen given but cannot cause human disease
  • Ex. Smallpox & Cowpox
  • Ex. M. tuberculosis (TB) and M. bovis (BCG)
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14
Q

Live Vaccine

Advantages

A
  • Smaller doses required
  • Stimulate immune response @ natural portal of entry
  • Induces wide spectrum of responses
    • More effectively mimic a natural immunity
  • Longer long-lasting immunity
    • Less frequent boosting
  • Usu. cheaper
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15
Q

Live Vaccines

Disadvantages

A
  • Safety issues
    • Reversion of virulence
      • Oral polio vaccine combines w/ Sabin to regain virulence
    • Contamination
      • Lubeck diaster ⇒ BCG vaccine contaminated w/ wild-type TB
      • Yellow fever w/ HBV
  • Viral interference ⇒ competition from other viruses either natural or in vaccines
  • Hard to store
  • Side effects
  • Vaccine related illnesses
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16
Q

Live Vaccines

Contraindications

A
  1. Immunosuppressed individuals
  2. Pregnant women
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17
Q

Whole Killed

Vaccines

A
  • Whole inactivated organisms
    • Formalin, acetone, heat, irradiation
  • Retained immunogenicity ⇒ induces a protective immune response
  • Unable to replicate
  • Lost ability to cause disease
  • Ex. poliovirus, influenza virus, 1st gen Bordetella pertussis
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18
Q

Subunit Vaccines

A

Specific component of organism containing necessary Ag determinants to elicit a protective immune response

Types:

  • Toxoids
  • Purified capsular polysaccharides
  • Recombinant antigens
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19
Q

Toxoid

Vaccines

A
  • Inactivated toxins
  • Induces neutralizing Ab to prevent toxin-mediated damage
  • Does not prevent infection
  • Ex. Diphtheria, tetanus, pertussis (acellular)
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20
Q

Purified Capsular Polysaccharide

Vaccines

A
  • Induce opsonizing Ab ⇒ promote phagocytosis and killing
  • Infants do not respond well ⇒ T-cell independent
  • Capsular polysaccharide + protein carrier used for infants ⇒ hapten-carrier effect
    • Elicits CD4+ T-cell help for Ab production
  • Ex. Haemophilus influenzae (Hib), Strep. pneumoniae, Neisseria meningiditis
21
Q

Conjugate

Vaccines

A

Capsular polysaccharide + protein carrier

  • Polysaccharide capsular Ag
    • Target Ag for B-cell response
    • Production of opsonizing Ab
  • Protein Carrier
    • Target Ag for T-cell response
    • Elicits CD4+ T-cell help for Ab production
  • Hapten-carrier effect
  • Used for infants
22
Q

Recombinant Antigen

Vaccines

A
  • Purified recombinant major surface protein
  • Made using recombinant DNA in euk/prok systemis
  • Induces neutralizing or opsonizing Ab
  • Ex. Hep B surface Ag, Borrelia burgdorferi (Lyme’s)
23
Q

Inactivated and Subunit Vaccines

Advantages

A
  • Safer ⇒ no reversion
  • Increased stability during storage
  • Little interference from other viruses
24
Q

Inactivated and Subunit Vaccines

Disadvantages

A
  • Large amount of Ag required
  • Requires adjuvants
  • Limited range of immune responses induced
    • Do not necessarily mimic natural immunity
  • Low immunogenicity w/ shorter duration of protection
    • Multiple booster shots usually needed
  • Must have well-defined target Ag ⇒ limited complexity
  • Subunit not always as effective as whole, killed vaccine
    • Ex. influenza
25
Q

Adjuvants

A
  • Components that non-specifically enhance immune responses
    • Purified PAMPs
      • Monophosphoryl lipid A
      • Muramyl dipeptide
      • CpG DNA
      • Cytokines
    • Stimulates PRRs ⇒ TLR’s
  • Stimulates APC’s
    • Mφ and dendritic cells in draining LN
    • ↑ cytokine production & costimulatory molecules
  • Modulate balance of Th1 vs Th2 type responses
  • Antigen depot effect ⇒ slow, sustained Ag release
    • Aluminum salts
    • Oil in water emulsions
  • Usually needed for subunit vaccines
  • Tend to be responsible for minor, local side effects
26
Q

Live Attenuated & Recombinant Virus Vaccines

Immune Response

A
  • Endogenous (MHC I) and exogenous (MHC II) Ag processing pathways potentially involved
  • CD8+ T-cells, CD4+ T-cells, and B-cells activated
27
Q

Whole Killed and Subunit Vaccines

Immune Response

A
  • 1° involves exogenous Ag processing pathway
  • CD4+ T-cells and B-cells activated
  • Difficult to prime CD8+ T-cells
28
Q

DNA Vaccines

A
  • Introduce plasmid DNA encoding pathogen Ag directly into host tissue
  • Host cells take up the DNA, express, and present Ag
    • Endogenous Ag processing pathway
  • Immunogenicity improved by:
    • Adding DNA plasmids encoding cytokines or co-stimulatory molecules
    • Novel delivery methods to enhance uptake ⇒ electroporation
  • Currently experimental
29
Q

Live Vectors

A
  • Introduce microbial genes into non-cytopathic virus or bacteria as vector
  • Organism replicates and produces protein ⇒ self-replicating vaccine
  • Ex. Advenovirus, poxviruses, attenuated Samonella or Listeria
  • Currently experimental
30
Q

Heterologous Prime-Boost

Strategies

A
  • Method:
    • Priming immunization w/ DNA based vaccine
    • Second booster immunization w/ live, viral vectored vaccine
  • ↑ immunogenicity of subunit vaccines
  • Focuses immune response on vaccine Ag
31
Q

Vaccine

Regulation

A
  • CDC and FDA
    • Maintain national surveillance system
    • Monitor safety and side effects after licensure
  • Vaccine Adverse Event Reporting system (VAERS)
    • Online tool for providers and pts to report any problems or side effects
32
Q

Public Health

Considerations

A
  • Vaccine-preventable illness still prevalent
  • Not all vaccines are 100% effective
  • Vaccine-preventable diseases occur in developed countries
    • Immunization programs neglected
    • ↓ compliance w/ recommendations
    • Concerns of real or perceived safety issues
  • Immunization programs in developing countries limited
    • Cost
    • Limited resources
    • Inadequate healthcare infrastructure
33
Q

Hep B

Vaccine

A

Recombinant HbsAg

34
Q

Haemophilus influenzae type B

Vaccine

A

Polysaccharide/protein conjugate

35
Q

Polio

Vaccine

A

Whole killed virus

(3 strains)

36
Q

DTaP

Vaccine

A

Diphtheria & tetanus ⇒ toxids

Pertussis ⇒ acellular (toxoids + adhesins)

37
Q

MMR

Vaccine

A

Measles, mumps, and rubella

Live attenuated virus

38
Q

Varicella

Vaccine

A

Live attenuated virus

39
Q

Neisseria meningitidis

Vaccine

A

Polysaccharide

40
Q

Rotavirus

Vaccine

A

Live attenuated virus

41
Q

Influenza

Vaccine

A

Trivalent inactivated (TIV)

or

Live attenuated (LAIV)

42
Q

Recommended Childhood Vaccines

Summary

A
43
Q

Strep. pneumoniae

Vaccine

A

Polysaccharide ⇒ over 60 y/o

Conjugate ⇒ infants

44
Q

HPV

Vaccine

A

Subunit (virus-like particle) ⇒ adolescent children

45
Q

Rabies

Vaccine

A

Inactivated virus

Given for recent bite, vets, animal caretakers.

46
Q

Yellow Fever

Vaccine

A

Live attenuated

Given for travel to endemic areas.

47
Q

Hep A

Vaccine

A

Killed virus

Given for travel to endemic areas.

48
Q

Salmonella typhi

Vaccine

A

Live attenuated or killed

Given for travel to endemic areas.

2. HDS Pulmonary (28 decks)

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