VACCINEVACCINE
Active vs. Passive ImmunizationActive vs. Passive Immunization
Designing VaccinesDesigning Vaccines
Whole-Organism VaccinesWhole-Organism Vaccines
Purified Macromolecules as VaccinesPurified Macromolecules as Vaccines
Recombinant-Vector VaccinesRecombinant-Vector Vaccines
DNA VaccinesDNA Vaccines
Synthetic-Peptide VaccinesSynthetic-Peptide Vaccines
Mulvivalent Subunit VaccinesMulvivalent Subunit Vaccines
Two Types of ImmunizationTwo Types of Immunization
Passive ImmunizationPassive Immunization
–Methods of acquisition include natural maternal antibodies, Methods of acquisition include natural maternal antibodies,
antitoxins, and immune globulinsantitoxins, and immune globulins
–Protection transferred from another person or animalProtection transferred from another person or animal
Active ImmunizationActive Immunization
–Methods of acquisition include natural infection, vaccines (many Methods of acquisition include natural infection, vaccines (many
types), and toxoidstypes), and toxoids
–Relatively permanentRelatively permanent
Acquisition of Passive and Active Acquisition of Passive and Active
ImmunityImmunity
Passive ImmunizationPassive Immunization
Can occur naturally via transfer of maternal antibodies across placenta to Can occur naturally via transfer of maternal antibodies across placenta to
fetusfetus
Injection with preformed antibodies Injection with preformed antibodies
–Human or animal antibodies can be usedHuman or animal antibodies can be used
–Injection of animal Ab’s prevalent before vaccinesInjection of animal Ab’s prevalent before vaccines
Effects are only temporaryEffects are only temporary
Conditions Warranting Passive Conditions Warranting Passive
ImmunizationImmunization
1.1.Deficiency in synthesis of Ab as a result of congenital or acquired Deficiency in synthesis of Ab as a result of congenital or acquired
B-cell defectsB-cell defects
2.2.Susceptible person is exposed to a disease that will cause Susceptible person is exposed to a disease that will cause
immediate complications (time is the biggest issue)immediate complications (time is the biggest issue)
3.3.Disease is already presentDisease is already present
Common Agents For Passive Common Agents For Passive
ImmunizationImmunization
The Immune System and Passive The Immune System and Passive
ImmunizationImmunization
The transfer of antibodies will not trigger the immune systemThe transfer of antibodies will not trigger the immune system
There is NO presence of memory cellsThere is NO presence of memory cells
Risks are includedRisks are included
Recognition of the immunoglobulin epitope by self immunoglobluin paratopes Recognition of the immunoglobulin epitope by self immunoglobluin paratopes
Some individuals produce IgE molecules specific for passive antibody, leading Some individuals produce IgE molecules specific for passive antibody, leading
to mast cell degranulationto mast cell degranulation
Some individuals produce IgG or IgM molecules specific for passive antibody, Some individuals produce IgG or IgM molecules specific for passive antibody,
leading to hypersensitive reactionsleading to hypersensitive reactions
Active ImmunizationActive Immunization
Natural Infection with Natural Infection with
microorganism or artificial microorganism or artificial
acquisition (vaccine)acquisition (vaccine)
Both stimulate the proliferation of T Both stimulate the proliferation of T
and B cells, resulting in the and B cells, resulting in the
formation of effector and formation of effector and memorymemory
cellscells
The formation of memory cells is The formation of memory cells is
the basis for the relatively the basis for the relatively
permanent effects of vaccinationspermanent effects of vaccinations
Principles Underlying VaccinationPrinciples Underlying Vaccination
Concept of ImmunityConcept of Immunity
–Self vs. Non-selfSelf vs. Non-self
–Antigen specificityAntigen specificity
–Indicated by presence of effector cellsIndicated by presence of effector cells
–Protection from infectious diseases using above Protection from infectious diseases using above
methodsmethods
VaccinationsVaccinations
Boosters (multiple inoculations) are required
Interference of passive maternal antibodies
Effectiveness of VaccinationsEffectiveness of Vaccinations
Small percentage of recipients will respond poorlySmall percentage of recipients will respond poorly
–Role of genetic determinants Role of genetic determinants
Herd ImmunityHerd Immunity
–Majority of population is immune, so chance of susceptible individual Majority of population is immune, so chance of susceptible individual
contacting infected individual is lowcontacting infected individual is low
–Measles EpidemicMeasles Epidemic
Herd ImmunityHerd Immunity
Factors affecting herd immunityFactors affecting herd immunity
–Environmental Factors: crowded conditions, seasonal variationsEnvironmental Factors: crowded conditions, seasonal variations
–Strength of Individual’s Immune SystemStrength of Individual’s Immune System
–Infectiousness of Disease: greater the risk of infection, the higher Infectiousness of Disease: greater the risk of infection, the higher
percentage of people need vaccines to attain herd immunitypercentage of people need vaccines to attain herd immunity
When enough people are vaccinated, chance of germ infecting the When enough people are vaccinated, chance of germ infecting the
non-immunized population is smallnon-immunized population is small
Can lead to disappearance of diseases (smallpox)Can lead to disappearance of diseases (smallpox)
–Vaccination no longer necessaryVaccination no longer necessary
Development of VaccinesDevelopment of Vaccines
Common misconception that Common misconception that
activation of the immune system results activation of the immune system results
in protective immunityin protective immunity
Multiple factors affect decisions Multiple factors affect decisions
when making vaccineswhen making vaccines
1. Activation of specific branch 1. Activation of specific branch
of immune systemof immune system
2. Development of 2. Development of
immunological memoryimmunological memory
Role of Memory CellsRole of Memory Cells
Depends on incubation period of pathogenDepends on incubation period of pathogen
–Short Incubation PeriodsShort Incubation Periods
ex. Influenzaex. Influenza
Symptoms already under way by the time memory cells are Symptoms already under way by the time memory cells are
activatedactivated
Repeated immunizations with neutralizing antibodiesRepeated immunizations with neutralizing antibodies
–Long Incubation PeriodsLong Incubation Periods
ex. Poliovirusex. Poliovirus
Enough time to allow memory B cells to respondEnough time to allow memory B cells to respond
Immunological Memory vs. Serum Immunological Memory vs. Serum
Antibody LevelsAntibody Levels
Whole-Organism VaccinesWhole-Organism Vaccines
Many common vaccines used Many common vaccines used
consist of inactivated or attenuated consist of inactivated or attenuated
bacterial cells or viral particlesbacterial cells or viral particles
Includes attenuated and inactivated Includes attenuated and inactivated
vaccinesvaccines
Attenuated Viral or Bacterial Attenuated Viral or Bacterial
VaccinesVaccines
Attenuation – to reduce in force, value, amount, or degree; weakenAttenuation – to reduce in force, value, amount, or degree; weaken
–Achieved by growth under abnormal culture conditionsAchieved by growth under abnormal culture conditions
–Bacillus Calmette-Guerin (BCG)Bacillus Calmette-Guerin (BCG)
–Act as a double edged sword, as they have distinct advantages and Act as a double edged sword, as they have distinct advantages and
disadvantages…disadvantages…
Advantages of Attenuated Bacterial Advantages of Attenuated Bacterial
or Viral Vaccinesor Viral Vaccines
Advantages stem from their capacity for transient growthAdvantages stem from their capacity for transient growth
Prolonged immune-system exposureProlonged immune-system exposure
Single immunizationsSingle immunizations
Replication within host cellsReplication within host cells
Exception to the Rule…Exception to the Rule…
Sabin Polio vaccine consists of 3 attenuated strains of poliovirusSabin Polio vaccine consists of 3 attenuated strains of poliovirus
Colonization of intestine results in immunity to all 3 strainsColonization of intestine results in immunity to all 3 strains
–Production of secretory IgA and induction of IgM and IgGProduction of secretory IgA and induction of IgM and IgG
Result is the need for boostersResult is the need for boosters
–Individual strains interfere with one anotherIndividual strains interfere with one another
First immunization First immunization one strain predominates in growth one strain predominates in growth
Second Immunization Second Immunization immunity generated by previous immunity generated by previous
immunization limits growth of previously predominant strainimmunization limits growth of previously predominant strain
Third Immunization Third Immunization same principle as second immunization same principle as second immunization
Disadvantages of Attenuated Disadvantages of Attenuated
Bacterial or Viral VaccinesBacterial or Viral Vaccines
MAJOR disadvantage is possible reversionMAJOR disadvantage is possible reversion
–ex: Rate of reversion of Sabin Polio vaccine is one case in 4 million dosesex: Rate of reversion of Sabin Polio vaccine is one case in 4 million doses
Presence of other viruses as contaminantsPresence of other viruses as contaminants
Unforeseen postvaccine complicationsUnforeseen postvaccine complications
Inactivated Viral or Bacterial Inactivated Viral or Bacterial
VaccinesVaccines
Methods of inactivation include heat or chemical agentsMethods of inactivation include heat or chemical agents
–End result…. Loss of replication abilityEnd result…. Loss of replication ability
Difficult to inactivate due to potential for denaturation of epitopesDifficult to inactivate due to potential for denaturation of epitopes
–Dependence on higher order levels of protein structureDependence on higher order levels of protein structure
Attenuation vs. InactivationAttenuation vs. Inactivation
Attenuation vs. InactivationAttenuation vs. Inactivation
AttenuationAttenuation
–Normally require one dosage to induce relatively permanent immunityNormally require one dosage to induce relatively permanent immunity
–Primarily cell-mediated in naturePrimarily cell-mediated in nature
–Despite reliance on cell-mediated immunity, increased IgA responseDespite reliance on cell-mediated immunity, increased IgA response
InactivationInactivation
–Requires multiple boostersRequires multiple boosters
–Emphasis on activating humoral immunityEmphasis on activating humoral immunity
However, something very important is missing….However, something very important is missing….