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Immune prophylaxis and Immunotherapy. Immune prophylaxis. I. Introduction. The last known person in the world to have a natural case of smallpox. Variola minor in 23-year-old Ali Maow Maalin, Merka, Somalia CDC In 1980, WHO announced that smallpox has been eradicated in the world.
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The last known person in the world to have a natural case of smallpox. Variola minor in 23-year-old Ali Maow Maalin, Merka, Somalia CDC • In 1980, WHO announced that smallpox has been eradicated in the world.
III. Artificial active immunization • Antigen:Vaccine or Toxoid • inactivated vaccine (Dead vaccine ) • Live-attenuated vaccine • Toxoid • Recombinant Vaccine:HBsAg
Agents used in active immunization • The agent used for artificial active immunization is called vaccine. • inactivated vaccine (Dead vaccine ) Standard strain of a microbe is killed and severed as an immunogen. For example: cholera vaccine Japanese encephalitis vaccine rabies vaccine typhoid vaccine
Agents used in active immunization • 2. Live-attenuated vaccine • It is more effective than dead vaccine • I.E:Bacillus Calmette-Guerin (BCG) vaccine;Measles virus vaccine;Polio virus vaccine (oral);Typhoid vaccine (oral live attenuated bacteria)
Tuberculin Skin Test • A tuberculin skin test is done to see if you have ever had tuberculosis (TB).
Live vaccine dead vaccine Comparison between live and dead vaccines Route of administration imitating natural injecting infection subcutaneously Doses of administration small large Times of administration once twice or more Side effect slight severe Duration of immunity long short 3~5 years several months~1 year Mutation possible impossible Preservation of vaccine at 4C easy to preserve or lyophilization
3. Toxoid • Exotoxin can be converted into nontoxic but still immunogenic preparations called toxoid. • Examples:Diphtheria toxoid, Tetanus toxoid
IV. Artificial passive immunization • Abs:Antitoxin,Human Ig(IMIG,IVIG,Specific Ig,McAb) • Cytokines(IL-2, IFN, CSF) • Cells(LAK,TIL).
Active immunization Passive immunization Comparison between active and passive immunization Administration Ag (vaccines, toxoid) Ab (antitoxin, -globulin) Production of slowly immediately immunity Duration of long (from several short (2 weeks to immunity months to years) months) Usage immunoprophylaxis emergency prophylaxis and therapy
V. Adjuvant • A substance that, when mixed with an immunogen, enhances the immune response against the immunogen.
VI. Planned immunization • A rational program of immunization against infectious diseases has been committed in children worldwide when many of the most damaging and preventable infections normally appear. • The program of childhood immunization is called planned immunization.
Age Type of vaccine Primary Immunization Birth BCG vaccine, HBV vaccine (1st) 1 month HBV vaccine (2nd) 2 months Poliovirus vaccine (1st) 3 months Poliovirus vaccine (2nd), DTP (1st) 4 months Poliovirus vaccine (3rd), DTP (2nd) 5 months DTP (3rd) 6 months HBV (3rd), Meningococcal polysaccharide vaccine 8 months Measles virus vaccine 1 year Japanese encephalitis vaccine (1st and 2nd) Booster/ reimmunization 1.5 years DTP, Measles virus vaccine, Poliovirus vaccine, Meningococcal polysaccharide vaccine 2 years Japanese encephalitis vaccine 3 years Japanese encephalitis vaccine 4 years Poliovirus vaccine 5 years DTP, Measles virus vaccine, BCG vaccine, Meningococcal polysaccharide vaccine Planned immunization schedule in China
VII. Development of novel vaccines • Subunit vaccine • These vaccines are in use which make use of antigens either purified from microorganisms or produced by recombinant DNA technology. • e.g. HBV vaccine (HBsAg)
Conjugate vaccine • These vaccines are obtained by conjugating the purified polysaccharides (bacterial capsular polysaccharides) to carrier proteins such as diphtheria toxoid.
Synthetic peptide vaccine • Small antigens can be made synthetically. e.g. HBs vaccine • Synthetic B-and T-cell epitopes can be combined in various ways to optimize the resulting immune response.
Genetic engineering vaccine • Recombinant antigen vaccine • Recombinant vector vaccine • DNA vaccine • Transgenic plant vaccine
Reverse vaccinology for identification novel vaccine antigen
VIII. Challenge of vaccines HIV HCV TB Malaria
II. Molecular Immunotherapy 1. Molecular Vaccine • Synthetic peptide vaccine • Recombinant vector vaccine • DNA vaccine used as treatment of tumor and infection
II. Molecular Immunotherapy 2. Antibody-polyclonal Ab • antitoxic serum • placental gamma-globulin • antibacterial immune serum • antiviral immune serum • anti-lymphocyte gamma-globulin, ALG
II. Molecular Immunotherapy 2. Antibody-Monoclonal antibody, mAb • mAb against surface membrane molecules on lymphocytes:CD3 • mAb against cytokines:TNF • mAb-directed therapy mAb coupled to isotopes, drugs, toxins
Application of Ab in vitro: elimination of cancer cells in bone marrow or T cells to prevention GVHD
Examples of tumor antigens that have been targeted by monoclonal antibodies in therapeutic trials.
II. Molecular Immunotherapy 2. Antibody-Genetic engineering Ab • Chimeric Ab • Humanized Ab (CDR-grafted Ab) • Single chain Ab • Bispecific Ab
II. Molecular Immunotherapy 3. Cytokines and their antagonists • Cytokine supplement and addition therapy IFN, IL-2, CSF • Cytokine blockade and suppression anti-TNF IL-1Ra sIL-1R
III. Cellular Immunotherapy • Cellular Vaccine • Tumor cellular vaccine • Gene-modified cancer vaccine • APC vaccine
III. Cellular Immunotherapy 2. Adoptive immunotherapy • TIL • LAK(CIK) 3. Stem cell transplantation • Bone marrow • Peripheral blood • Umbilical blood
VI. Biological response modifier and immunosuppressive agent 1. Biological response modifier(BRM) A variety of agents that stimulate the immune response non-specifically are called biological response modifier. • Microorganism products: BCG, corynebacterium parvum (CP), polysaccharide • Synthetic molecules:polyI:C • CK • Hormones:Thymosin, Thymopoietin
Immunosuppressive agents 1. Chemicals Glucocorticoids, cyclophosphamide, azothioprine,etc.
Immunosuppressive agents 2. Microorganism products Cyclosporin, FK506, rapamycin