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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 23year-old Ali Maow Maalin, Merka, Somalia CDC •In 1980, WHO announced that smallpox has been eradicated in the world. II. Essential requirements of vaccine III. Artificial active immunization  Antigen:Vaccine or Toxoid  inactivated vaccine (Dead vaccine )  Live-attenuated vaccine  Toxoid  Recombinant Vaccine:HBsAg Agents used in active immunization  1. 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) Live attenuated vs inactivated Vaccines Live-attenuated Vaccines Route imitating natural infection Doses Times Side effects Duration small once slight Long (3~5years or life long) possible 4C or lymphilization Mutation Preservation Inactivated Vaccines Injection subcutaneously Large Twice or more severe Short (months~1 years) impossible easy to preserve Live attenuated vs inactivated Vaccines Jonas Salk Albert Sabin 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). Comparison between active and passive immunization Active immunization Administration Ag (vaccines, toxoid) slowly Passive immunization Ab (antitoxin, globulin) immediately Production of immunity Duration of immunity long (from several months to years) short (2 weeks to months) Usage immunoprophylaxis emergency prophylaxis and therapy V. Adjuvant   A substance that, when mixed with an immunogen, enhances the immune response against the immunogen. Alum 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. Planned immunization schedule in China Primary Immunization Booster/ reimmunization Age Type of vaccine 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) 1.5 years DTP, Measles virus vaccine, Poliovirus 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 vaccine, 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 • Synthetic peptide vaccine • Genetic engineering vaccine  Recombinant antigen vaccine  Recombinant vector vaccine  DNA vaccine  Transgenic plant vaccine Reverse vaccinology for identification novel vaccine antigen Preventative Vaccine Therapeutic Vaccine VIII. Challenge of vaccines HIV HCV TB Malaria Immunotherapy I. Conception and classification Name Scope or Characteristic immunoenhancing therapy Infection, Tumor, IDD immunosuppressive therapy HVGR, GVHR, AID, Anaphylaxis, Inflammation active immunotherapy passive immunotherapy Vaccine,Therapeutic Vaccine of tumor, Ab, LAK cell specific immunotherapy Peptide,antigen, Non-specific immunotherapy BCG, cytokines 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, CD20, 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 1. Cellular Vaccine  Tumor cellular vaccine   Gene-modified cancer vaccine APC vaccine 基于DC的免疫学治疗 浙江大学 40 III. Cellular Immunotherapy 2. Adoptive immunotherapy TIL  LAK(CIK) 3. Stem cell transplantation  Bone marrow  Peripheral blood  Umbilical blood  肿瘤浸润性淋巴细胞治疗 42 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. 2. Microorganism products Cyclosporin, FK506, rapamycin Summary   Classification of immunoprophylaxis and their biological materials Classification of immunotherapy and their biological materials Happy Halloween