1. Immune prophylaxis and Immunotherapy

2. Immune prophylaxis

3. I. Introduction

4. 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.

5. II. Essential requirements of vaccine

6. III. Artificial active immunization  Antigen:Vaccine or Toxoid  inactivated vaccine (Dead vaccine )  Live-attenuated vaccine  Toxoid  Recombinant Vaccine:HBsAg

7. Agents used in active immunization  The agent used for artificial active immunization is called vaccine. 1. 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

8. 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)

9. Tuberculin Skin Test  A tuberculin skin test is done to see if you have ever had tuberculosis (TB).tuberculosis (TB) Normal (negative results):No TB infection, No BCG vaccinantion positivePost TB infection; BCG vaccinantion Strong PositiveActive TB infection

10. Live vaccine dead vaccine 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 4  C easy to preserve or lyophilization Comparison between live and dead vaccines

11. 3. Toxoid  Exotoxin can be converted into nontoxic but still immunogenic preparations called toxoid.  Examples:Diphtheria toxoid, Tetanus toxoid

12. IV. Artificial passive immunization  Abs:Antitoxin,Human Ig(IMIG,IVIG,Specific Ig,McAb)  Cytokines(IL-2, IFN, CSF)  Cells(LAK,TIL).

14. Active immunization 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 Comparison between active and passive immunization

15. V. Adjuvant  A substance that, when mixed with an immunogen, enhances the immune response against the immunogen.

18. 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.

19. Planned immunization schedule in China AgeType of vaccine Primary Immunization BirthBCG vaccine, HBV vaccine (1 st ) 1 monthHBV vaccine (2 nd ) 2 monthsPoliovirus vaccine (1 st ) 3 monthsPoliovirus vaccine (2 nd ), DTP (1 st ) 4 monthsPoliovirus vaccine (3 rd ), DTP (2 nd ) 5 monthsDTP (3 rd ) 6 monthsHBV (3 rd ), Meningococcal polysaccharide vaccine 8 monthsMeasles virus vaccine 1 yearJapanese encephalitis vaccine (1 st and 2 nd ) Booster/ reimmunization 1.5 yearsDTP, Measles virus vaccine, Poliovirus vaccine, Meningococcal polysaccharide vaccine 2 yearsJapanese encephalitis vaccine 3 yearsJapanese encephalitis vaccine 4 yearsPoliovirus vaccine 5 yearsDTP, Measles virus vaccine, BCG vaccine, Meningococcal polysaccharide vaccine

20. 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)

21. Conjugate vaccine  These vaccines are obtained by conjugating the purified polysaccharides (bacterial capsular polysaccharides) to carrier proteins such as diphtheria toxoid.

23. 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.

25. Genetic engineering vaccine  R ecombinant antigen vaccine  Recombinant vector vaccine  DNA vaccine  Transgenic plant vaccine

27. Reverse vaccinology for identification novel vaccine antigen

28. Preventative Vaccine

29. Therapeutic Vaccine

30. VIII. Challenge of vaccines HIV HCV TB Malaria

32. Immunotherapy

33. I. Conception and classification NameScope or Characteristic immunoenhancing therapyInfection, Tumor, IDD immunosuppressive therapyHVGR, GVHR, AID, Anaphylaxis, Inflammation active immunotherapyVaccine,Therapeutic Vaccine of tumor, passive immunotherapyAb, LAK cell specific immunotherapyPeptide,antigen, Non-specific immunotherapyBCG, cytokines

34. II. Molecular Immunotherapy 1. Molecular Vaccine  Synthetic peptide vaccine  Recombinant vector vaccine  DNA vaccine used as treatment of tumor and infection

35. II. Molecular Immunotherapy 2. Antibody-polyclonal Ab  antitoxic serum  placental gamma-globulin  antibacterial immune serum  antiviral immune serum  anti-lymphocyte gamma-globulin, ALG

36. 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

37. Application of Ab in vitro: elimination of cancer cells in bone marrow or T cells to prevention GVHD

38. Examples of tumor antigens that have been targeted by monoclonal antibodies in therapeutic trials.

39. II. Molecular Immunotherapy  Chimeric Ab  Humanized Ab (CDR-grafted Ab)  Single chain Ab  Bispecific Ab 2. Antibody-Genetic engineering Ab

41. II. Molecular Immunotherapy  Cytokine supplement and addition therapy IFN, IL-2, CSF  Cytokine blockade and suppression anti-TNF IL-1Ra sIL-1R 3. Cytokines and their antagonists

43. III. Cellular Immunotherapy 1. Cellular Vaccine  Tumor cellular vaccine  Gene-modified cancer vaccine  APC vaccine

45. III. Cellular Immunotherapy 2. Adoptive immunotherapy  TIL  LAK （ CIK ） 3. Stem cell transplantation  Bone marrow  Peripheral blood  Umbilical blood

46. 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

47. Immunosuppressive agents 1. Chemicals Glucocorticoids, cyclophosphamide, a zothioprine, etc.

49. Immunosuppressive agents 2. Microorganism products Cyclosporin, FK506, rapamycin

52. Summary  Classification of immunoprophylaxis and their biological materials  Classification of immunotherapy and their biological materials

53. Thank you for your attention! chenjianzhong@zju.edu.cn