ACTIVE AND PASSIVE IMMUNIZATION

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

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.

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

The eradication of smallpox by vaccination

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

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

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

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. * * * * * * * * *

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

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

Generation of attenuated viruses by tools of molecular biology

A successful vaccination campaign against Polio

Childhood mortality from rotavirus infection in the 10 most affected countries

Two effective rotavirus vaccines

Attenuation vs. Inactivation

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

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

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

Some adjuvants licensed for use in human vaccin

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

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

DNS vaccines

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)

ANTIBODIES AGAINST DIPHTERIA AND TETANUS TOXINS (ANTITOXINS) Koch Laboratory, Germany, 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

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

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

 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)

(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

FEATURES OF POLYCLONAL AND MONOCLONAL ANTIBODIES

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

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;

Diseases for which vaccines are available

Diseases for which better vaccines are needed