Antimicrobial Vaccines Flashcards
Immunization Goals
- Prevent infection and/or reduce severity of disease in a given individual
-
Reduce transmission and if possible eradicate an infectious disease at the population level
- Herd immunity ⇒ possible if vaccine coverage high enough
Protective Responses
- ⊗ 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
Passive Immunization
Definition
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
Therapeutic
Passive Immunization
-
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
Passive Immunization
Pros and Cons
- 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
Passive Immunization
Examples
Active Immunization
Overview
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
Active Immunization
Requirements
Present protective Ag in appropriate context to promote immune recognition and response.
Expansion of protective, pathogen specific immune effector and memory lymphocytes.
Vaccine Success
-
Efficacy
- Nature and complexity of protective immune response
- Ability to elicit appropriate responses by immunization
- Duration of immunity
- Safety
- Stability
- Cost
Target Populations
Vaccine Classes
- Live attenuated
- Whole virus
- Cross-reactive
- Whole killed
- Subunit (several types)
Live Attenuated
Vaccines
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
Antigenically Cross-reactive
Vaccines
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)
Live Vaccine
Advantages
- 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
Live Vaccines
Disadvantages
-
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
-
Reversion of virulence
- Viral interference ⇒ competition from other viruses either natural or in vaccines
- Hard to store
- Side effects
- Vaccine related illnesses
Live Vaccines
Contraindications
- Immunosuppressed individuals
- Pregnant women
Whole Killed
Vaccines
-
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
Subunit Vaccines
Specific component of organism containing necessary Ag determinants to elicit a protective immune response
Types:
- Toxoids
- Purified capsular polysaccharides
- Recombinant antigens
Toxoid
Vaccines
- Inactivated toxins
- Induces neutralizing Ab to prevent toxin-mediated damage
- Does not prevent infection
- Ex. Diphtheria, tetanus, pertussis (acellular)
Purified Capsular Polysaccharide
Vaccines
- 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
Conjugate
Vaccines
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
Recombinant Antigen
Vaccines
- 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)
Inactivated and Subunit Vaccines
Advantages
- Safer ⇒ no reversion
- Increased stability during storage
- Little interference from other viruses
Inactivated and Subunit Vaccines
Disadvantages
- 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
Adjuvants
-
Components that non-specifically enhance immune responses
- Purified PAMPs
- Monophosphoryl lipid A
- Muramyl dipeptide
- CpG DNA
- Cytokines
- Stimulates PRRs ⇒ TLR’s
- Purified PAMPs
-
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
Live Attenuated & Recombinant Virus Vaccines
Immune Response
- Endogenous (MHC I) and exogenous (MHC II) Ag processing pathways potentially involved
- CD8+ T-cells, CD4+ T-cells, and B-cells activated
Whole Killed and Subunit Vaccines
Immune Response
- 1° involves exogenous Ag processing pathway
- CD4+ T-cells and B-cells activated
- Difficult to prime CD8+ T-cells
DNA Vaccines
- 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
Live Vectors
- 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
Heterologous Prime-Boost
Strategies
- 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
Vaccine
Regulation
-
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
Public Health
Considerations
- 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
Hep B
Vaccine
Recombinant HbsAg
Haemophilus influenzae type B
Vaccine
Polysaccharide/protein conjugate
Polio
Vaccine
Whole killed virus
(3 strains)
DTaP
Vaccine
Diphtheria & tetanus ⇒ toxids
Pertussis ⇒ acellular (toxoids + adhesins)
MMR
Vaccine
Measles, mumps, and rubella
Live attenuated virus
Varicella
Vaccine
Live attenuated virus
Neisseria meningitidis
Vaccine
Polysaccharide
Rotavirus
Vaccine
Live attenuated virus
Influenza
Vaccine
Trivalent inactivated (TIV)
or
Live attenuated (LAIV)
Recommended Childhood Vaccines
Summary
Strep. pneumoniae
Vaccine
Polysaccharide ⇒ over 60 y/o
Conjugate ⇒ infants
HPV
Vaccine
Subunit (virus-like particle) ⇒ adolescent children
Rabies
Vaccine
Inactivated virus
Given for recent bite, vets, animal caretakers.
Yellow Fever
Vaccine
Live attenuated
Given for travel to endemic areas.
Hep A
Vaccine
Killed virus
Given for travel to endemic areas.
Salmonella typhi
Vaccine
Live attenuated or killed
Given for travel to endemic areas.
