Prevention And Control - Passive And Active Immunization

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Prevention and Control –passive and active immunization

How do we acquire immunity?

Passive Immunity in Infants

Artificial Passive Immunity Gamma globulin– Ig’s from pooled blood of at least 1,000human donors variable content non-specific Specific immune globulin– higher titers of specific antibodies

Artificial Passive Immunity Gamma globulin– Ig’s from pooled blood of at least 1,000human donors variable content non-specific Specific immune globulin– higher titers of specific antibodies Antisera and antitoxins of animal origin

Risks of Passive ImmunizationIf Antibody is produced in another species, thehuman recipient can produce an ImmuneResponse against itIn some patients: IgE production against isotypicAb - systemic mast cell activation - type IhypersensitivityIn others ! IgM or IgG vs isotype - complementactivation - Type III hypersensitivity

How do we acquire immunity?

Artificial Active Immunity Vaccination (Immunization)– exposing a person to material that is anantigen but NOT pathogenic.

Phases of immune response

Designing vaccinesImportant questions to consider:1- Which part of the immune system should beactivated?2- Is immunologic memory sufficiently stimulated?This depends on the disease.- Influenza has a short incubation (1-2 d); effective immunity againstflu depends on maintaining high levels of Ig through repeatimmunizations- Polio virus has a longer incubation ( 3d) and gives memory cellstime to produce serum Ig and activate immune cell effectors

Childhood vaccines 7 major vaccines:––––HepBDTaP (Diphtheria, Tetanus, Pertussis)IPV (smallpox /vaiolo)MMR (measles, mumps, and rubella / morbillo,parotite, rosolia)– Hib (Haemophilus influenzae type B)– Var (Varicella)– PCV (Pneumococcal Conjugate Vaccine)*children require booster shots for most (American Academy of Pediatrics, 2002)

Adult vaccines(dependent on risk group) For those living in close quarters– Meningitis (Hib)– Pneumonia (PCV)– Influenza For travelers to endemic ingitsYellow feverPolio

Large scale vaccination programs Dramatic improvements inpublic health. Nobody in this room hashad – Smallpox, Polio, Measles,Chickenpox– Mumps, Rubella Because of vaccination Smallpox is the onlyhuman disease to ever beeradicated

Characteristics of a good vaccine Safe / Few side effectsGive long lasting, appropriate protectionLow in costStable with long shelf life (no special storagerequirements) Easy to administer Public must see more benefit than risk

Types of vaccines whole agent subunit of the agent– recombinant– individual parts alone

Whole agent vaccinesKilled using heat or formaldehydeLive virusKilled virusepitopesepitopesInactivated polio vaccine (Salk)Influenza (Classic)

Whole agent vaccines Attenuated attenuated - a process that lessens thevirulence of a microbeoral polio vaccine (Sabin),MMR (measles, mumps, rubella)Influenza -- Flumist

Attenuation of viruses by passagethrough non-human cells12341. Pathogenic virus isolated frompatient, grown in human cells2. Infect monkey cells with culturedvirus3. Virus acquires many mutationsthat allow it to grow well inmonkey cells4. Mutations make the virus unableto grow well in human cells! Vaccine candidate

Construction of recombinant attenuated virus1.2.3.4.Isolate virusClone genomeIsolate virulence geneMutate or delete virulencegene5. Resulting virus is Viable Immunogenic Not virulent Can be used as a vaccine

Vaccines stimulate immune memory Killed virus vaccine requires multiple doses(booster shots) to adequately stimulate aprotective immune response Live virus vaccines replicate in the host. No requirement for boosters.

Vaccines stimulate immune memory Killed virus vaccine requires multiple doses(booster shots) to adequately stimulate aprotective immune response Live virus vaccines replicate in the host. No requirement for boosters.

Advantages for live vaccines– multiply like natural organism– require fewer doses and boosters– long-lasting Disadvantages for live vaccines– special storage– back mutation– side effects

Subunit vaccines Single antigen or mixture of antigens Safer (cannot reproduce) However, often less effective thanwhole agent vaccines Can be costly Always require boosters

Overcoming Subunit vaccineproblems1. Multiple doses2. Use adjuvants prolongs stimulation of immuneresponse works by trapping the antigens in achemical complex and releasesthem slowly

Types of vaccinesLivevaccinesLiveKilledAttenuated InactivatedvaccinesvaccinesToxoidsCellular fractionvaccines Small poxvariolavaccine BCG Typhoidoral Plague Oral polio Yellowfever Measles Mumps Rubella IntranasalInfluenza Typhus Diphtheria Tetanus Meningococcal Hepatitis Bpolysaccharide vaccinevaccine Pneumococcalpolysaccharidevaccine Hepatitis Bpolypeptidevaccine Typhoid Cholera Pertussis Plague Rabies Salk polio Intramuscularinfluenza JapaniseencephalitisRecombinantvaccines

Vaccine delivery systems and adjuvants

Vaccine delivery systems and adjuvantsISCOMS as peptide delivery systems

Vaccine delivery systems and adjuvants

Representative results of DNA vaccine trials

DNA vaccines Vs Traditional vaccinesDNA vaccines Uses only the DNA frominfectious organisms. Avoid the risk of usingactual infectiousorganism. Provide both Humoral &Cell mediated immunity Refrigeration is notrequiredTraditional vaccines Uses weakened or killedform of infectiousorganism. Create possible risk ofthe vaccine being fatal. Provide primarilyHumoral immunity Usually requiresRefrigeration.

DISADVANTAGES Limited to protein immunogen only Extended immunostimulation leads tochronic inflammation Some antigen require processingwhich sometime does not occur

Vaccine delivery systems and adjuvants

Routes of administration Deep subcutaneous or intramuscular route(most vaccines) Oral route (sabine vaccine, oral BCGvaccine) Intradermal route (BCG vaccine) Scarification (small pox vaccine) Intranasal route (live attenuated influenzavaccine)

Routes of administration Gene gun delivery:- Adsorbed plasmid DNA into goldparticles Ballistically accelerated into bodywith gene gun.

HOW DNA VACCINE WORKSBY TWO PATHWAYSENDOGENOUS :- Antigenic Protein is presented bycell in which it is producedEXOGENOUS :-Antigenic Protein is formed inone cell but presented by different cell

Scheme of immunization Primary vaccination– One dose vaccines (BCG, variola, measles,mumps, rubella, yellow fever)– Multiple dose vaccines (polio, DPT, hepatitis B) Booster vaccinationTo maintain immunity level after it declines aftersome time has elapsed (DT, MMR).

Periods of maintained immunity dueto vaccines Short period (months): cholera vaccineTwo years: TAB vaccineThree to five years: DPT vaccineFive or more years: BCG vaccineTen years: yellow fever vaccineSolid immunity: measles, mumps, andrubella vaccines.

Levels of effectiveness Absolutely protective(100%): yellow fevervaccine Almost absolutely protective (99%): Variola,measles, mumps, rubella vaccines, anddiphtheria and tetanus toxoids. Highly protective (80-95%): polio, BCG, HepatitisB, and pertussis vaccines. Moderately protective (40-60%) TAB, choleravaccine, and influenza killed vaccine.

Vaccination Coverage Vaccination coverage is the percent of atrisk or susceptible individuals, orpopulation who have been fully immunizedagainst particular diseases by vaccines ortoxoids. To be significantly effective inprevention of disease on mass orcommunity level at least a satisfactoryproportion (75% or more) of the “at risk”population must be immunized.

New approaches Cancer HIV/AIDS MalariaVaccines against bioterrorism Anthrax Small pox plague

Prevention and Control - passive and active immunization How do we acquire immunity? Passive Immunity in Infants Artificial Passive Immunity Gamma globulin - Ig's from pooled blood of at least 1,000 human donors variable content non-specific Specific immune globulin - higher titers of specific antibodies Artificial Passive Immunity

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