1. ACTIVE AND PASSIVE IMMUNIZATION

2. Two types of immunization Active immunization - natural infection - vaccination, that provides people with an immunological memory of a pathogen without them having to be infected by the pathogen and suffer the disease it causes Passive immunization - natural maternal antibodies - the injection of specific antibodies to provide protection against a pathogen or toxin. The administered antibodies may derive from human blood donors, immunized animals, or hybridoma cell lines

3. Edward Jenner The modern era of vaccination began in 1796 with Edward Jenner’s published report on how material from animals infected with cowpox, a disease of cattle, could be used as a vaccine to protect against smallpox.

4. Vaccination with cowpox virus elicits neutralizing antibodies that react with antigenic determinants shared with smallpox virus

5. The eradication of smallpox by vaccination

6. PRINCIPLES OF VACCINATION Goals: Prevent infection, transmission and/or disease Specificity: Generating an immune response against a specific pathogen Development of memory: prevents infection with the same or a similar pathogen

7. Characteristics of a good vaccine Safe Few side effects Give long lasting, appropriate protection Low in cost Stable with long shelf life (no special storage requirements) Easy to administer Public must see more benefit than risk

8. Types of vaccines Whole-Organism – Inactivated Viral/Bacterial – Attenuated Viral/Bacterial Purified Macromolecules – Polysaccharide – Toxoid – Recombinant Antigen Synthetic Peptide DNA

9. Inactivated Viral/Bacterial Vaccines These types of vaccines consist of pathogens that cannot replicate because they have been treated chemically with formalin or physically with heat or irradiation. * * * * * * * * *

10. Attenuated Viral or Bacterial Vaccines Attenuation - a process that lessens the virulence of a microbe * * * * * * * *

11. Attenuated viruses are selected by growing human viruses in non-human cells

12. Generation of attenuated viruses by tools of molecular biology

13. A successful vaccination campaign against Polio

14. Childhood mortality from rotavirus infection in the 10 most affected countries

15. Two effective rotavirus vaccines

16. Attenuation vs. Inactivation

17. Molecular complexes recognized by both B and T cells make effective vaccines Conjugate vaccines

18. toxin moiety antigenic determinants chemical modification ToxinToxoid Modification of Toxin to Toxoid (e.g. diphtheria toxin, tetanus toxin)

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

20. Some adjuvants licensed for use in human vaccin

21. Reverse vaccinology HLA-B53 has a protective effect against fatal cerebral malaria. Identification of peptides from Plasmodium falciparum binding to HLA-B53 Identification of peptides that induce strong CTL responses

22. Vaccination with Neisseria factor H-binding protein (fHbp) prevents infection from taking hold

23. DNS vaccines

24. SOME CONTRAINDICATIONS FOR VACCINATING  Do not give vaccines to actually ill patients  Do not give live vaccines to immunosuppressed patients  Avoid giving live vaccines to pregnant women  Avoid all types of vaccines in the first trimester of pregnancy  In spite of immune suppression in HIV infected patient, we can give MMR (measles, mumps, rubella) but not BCG (Bacillus Calmette–Guérin)

25. ANTIBODIES AGAINST DIPHTERIA AND TETANUS TOXINS (ANTITOXINS) Koch Laboratory, Germany, 1890. Investigations: Protective humoral factors (pathogen-specific antibodies) in the blood Many diseases occur only once (natural protection) Some diseases can be prevented by vaccination The blood contains anti-bacterial activity (anti-toxins  serum therapy) Emil Behring Shimbasaru Kitasato

26. MONOCLONAL ANTIBODIES monoclonal antibodies clones of a single B cell binding to a single epitope polyclonal antibodies clones of many B cells POLYCLONAL ANTIBODIES binding to multiple epitopes

27. POLYCLONAL ANTIBODIES AgAg Immunserum Polyclonal antibody AgAg Ag Set of B- cells Activated B- cells Antibody- producing plasma- cells Antigen-specific antibodies - Products of a set of B-lymphocyte clones - Heterogeneous in antigen specificity, affinity, and isotype

28.  Products of clones of one B-lymphocyte  Homogeneous in specificity, affinity, and isotype  Can be found in humans in a pathologic condition called multiple myeloma, which is a malignant proliferation of a plasma cell (see supplementary) MONOCLONAL ANTIBODIES (MAb)

29. (1) Immunization of a mouse (2) Isolation of B cells from the spleen (3) Cultivation of myeloma cells (4) Fusion of myeloma and B cells (5) Separation of cell lines (6) Screening of suitable cell lines (7) in vitro (a) or in vivo (b) multiplication (8) Harvesting STEPS OF MAb GENERATION

30. FEATURES OF POLYCLONAL AND MONOCLONAL ANTIBODIES

31. Mouse Chimeric Human Humanized *Humanized antibodies are from non-human species whose protein sequences have been modified to increase their similarity to antibody variants produced naturally in humans (except CDR loops)! DIFFERENT TYPES AND IMMUNOGENICITIES OF ANTIBODIES USED IN THERAPY

32. PASSIVE IMMUNIZATION TypeApplication Intramuscular (less effective due to lower dose) HBV-Ig; Varicella-zoster-Ig; Diphtheria and tetanus antitoxins. Intravenous (IVIG)Bruton-agammaglobulinaemia; Variable and mixed immunodeficiencies with hypogammaglobulinaemia; Anti-venom antibody treatment;

33. Diseases for which vaccines are available

34. Diseases for which better vaccines are needed