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Immunology 2008 Lecture 23 Vaccination 5 November. TODAY Vaccination, Chap. 22 Genetic Control (no core notes). Natural Immunity to Smallpox Known since antiquity Recovery from disease leads to immunity (smallpox et al .)
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Immunology 2008 Lecture 23 Vaccination 5 November
TODAY Vaccination, Chap. 22 Genetic Control (no core notes)
Natural Immunity to Smallpox Known since antiquity Recovery from disease leads to immunity (smallpox et al.) Specificity & Memory
Edward Jenner 1749-1823 1796 - Local milkmaid, Sarah Nelmes, diagnosed with cowpox. Jenner scratched material from pocks onto the arm of 8-year-old James Phipps. Showed mild symptoms & recovered. Six weeks later, Jenner inoculated James with smallpox – he developed no symptoms of disease!
Variolation: Inoculation with smallpox pustules, used in China in the 16th century, came to Europe in the 18th century. Effective, but mortality could be as high as ~10% Vaccination: Use of “attenuated” live organism, e.g. cowpox, far safer; published by Jenner in 1798 Vaccination has had a dramatic effect on reducing infant mortality and increasing life expectancy
Active vs. Passive Immunization Active: Recipient’s immune system generates response [humoral or cellular]following challenge with antigen(smallpox, DPT etc.) Passive: Recipient is made immune by transfer of antibodies [humoral]. (diphtheria & tetanus anti-toxins, etc.)). Animal antibodies - antitoxins, antivenins; danger of serum sickness & allergy Human antibodies - HBVIG, ZIG, decreased risk RhoGam - (Abs may suppress immune response) Adoptive: Transfer of immune cells - experimental systems [“Transfer Factor”(s) in humans…?]
Materials used for Vaccines Killed organisms(rabies, influenza, pertussis...) (+) Whole organisms, no risk of disease (-) Difficult to get CD8 response Attenuated organisms(smallpox, BCG, MMR, varicella...) (+) Live organisms, more effective CD8 response (-) Risk of disease Toxoids and other purified components(“subunit” vaccines) (+) Chemically defined, no risk of disease (-) Need to effectively choose target molecules & ensure responsiveness Recombinant & engineered products
Materials used for Vaccines (ctd.) Conjugates - microbial polysaccharides coupled to protein carrier. Convert TI to TD response, increased effectiveness in infants (<24 mos) Naked DNA - plasmid encoding antigenic peptide. Endogenous peptide processing, good CD8 response. (More effective in mice than humans…)
Smallpox Declared Eradicated in 1980(last known case in 1977) Some relevant factors: 1) Effective, life-long immunity 2) No carrier state (contrast with “Typhoid Mary”) 3) No non-human reservoir (e.g. Hanta, Ebola etc.) Can we do this with Polio? Measles? Yes…but limited by money, organization, politics.
Some Limitations on Vaccine Effectiveness Existence of multiple serotypes (e.g. rhinovirus). Antigenic variation (e.g. influenza, Borrelia, HIV). Antigenic competition - purely empirical; some vaccines work fine together (e.g. DPT), others don’t. Passive antibodyinterference – especially live virus (e.g. measles vaccine administered only after 14 months of age because of the possible presence of maternal antibody).
Adjuvants, Experimental vs. Clinical Freund’s Adjuvant, complete (water-in-oil emulsion + mycobacteria) Synthetic adjuvants, muramyl dipeptide (MDP) originally identified in CFA *Alum (Al2OH3), precipitated with antigen slow-releasing depot, effective phagocytosis *MF 59, squalene + oil/water emulsion (experimental) Immune Stimulatory Complexes (ISCOM) lipid micelles containing viral proteins – deliver to cytosol, MHC Class I presentation *used in humans
Recommended Vaccines *Poliomyelitis killed virus (Salk) [live virus (Sabin)] MMR Measles live virus Mumps live virus Rubella live virus DPT *Diphtheria toxoid *Tetanus toxoid *Pertussis killed bacteria *Hepatitis B recombinant Ag Pneumococcus conjugate Haemophilus B conjugate *Influenza killed virus Varicella live virus