(Immunization / Vaccination) Immunoprophylaxis (Immunization / Vaccination) It is the main objective of acquired immunity and represents one of the greatest accomplishment of biomedical sciences. It is of 3 types: Active acquired (Natural or Artificial) Passive acquired (Natural or Artificial). Active-Passive Immunity.

I. Active acquired immunity: On exposure to foreign antigen or infective agent, the individual actively produces his own antibodies or sensitized lymphocytes. Immunity develops slowly, but lasts for a long time due to development of immunological memory. It can be: 1. Natural active immunity: which occurs after clinical or subclinical infections, e.g., measles or mumps. 2. Artificial active immunity: that occurs After vaccination (see below).

II. Passive Acquired Immunity: In which ready made antibodies are transferred to an individual. This gives rapid protection, however, immunity is short lasting. There are TWO types : 1. Natural passive immunity: As occurs when antibodies are transferred from mother to foetus through the placenta (IgG) or in the breast milk in particular colostrum (IgA). This immunity is protective of the newborn against several diseases during the first 6 months after birth.

2. Artificial passive immunity: As in prophylaxis against several diseases; for example: A. Anti-Toxin against diphtheria or tetanus. B. Specific immunoglobulins (immune serum) for pre- or post-exposure prophylaxis in hepatitis A, B, or C , and protection of children (e.g., premature or immunodeficient) exposed to measles before vaccination.

III. Passive-Active Immunity: Involves giving both preformed antibodies to provide immediate protection and a vaccine (at the same time) to provide long term protection. They should be given at different sites of the body to prevent the antibodies from neutralizing the antigens of the vaccine. Example : post-exposure prophylaxis of susceptible individual to tetanus, rabies or hepatitis B.

Primary & Secondary Antibody Response Primary response: when an individual or animal is exposed to foreign antigen for the first time, the antibody (IgM) starts to appear after 7-10 days (Lag phase or induction period), then rises to peak within 2 weeks (exponential phase), followed by steady (plateau) phase, and then declines (declining phase) rapidly to undetectable level. Memory B- cells are generated.

Secondary response: On re-exposure to the same antigen (e. g Secondary response: On re-exposure to the same antigen (e.g. booster dose of vaccine) after weeks, months or even years of the primary exposure, the antibody response (mainly IgG with little IgM or others) will be more rapid (short Lag; several hours), reaches very high concentration & affinity (short exponential; 5-7 days), with longer steady and declining phases. The immunological memory is the cause of these differences between the two types of response. Note: Tell cell response have also primary & secondary responses with generation of Memory T-cells.

Vaccination (Immunization): The different types of vaccines are five: 1. Killed or inactive ,e.g., TAB (for typhoid and paratyphoid fevers), Salk vaccine (for poliomyelitis), and human rabies vaccine. This type of vaccines have the following concerns (problems): A. Immunity is short lasting & needs boosting. B. Poor (if any) in stimulating local immunity. C. In viral killed vaccine , the viruses do not replicate and do not stimulate cytotoxic cells. All of these problems are due to the preparative destruction (by heat or phenol) of most of the antigenic components (determinants) of the vaccine.

2. Living Attenuated vaccines, e. g 2. Living Attenuated vaccines, e.g., Sabin (polio), BCG (tuberculosis), MMR (Measles, Mumps & Rubella), and Rabies. In this type of vaccines most of the antigenic components are preserved during preparation and have the following concerns: A. Though they stimulate both humoral & cellular immunity both locally & systemically, but they may revert to virulence (cause disease). B. Should not be given to immunocom- promised hosts (low immunity) & pregnant women because of potential risk of infection (or damage) to host or foetus respectively.

C. The live vaccine can be excreted by the immunized person C. The live vaccine can be excreted by the immunized person. This can spread the vaccine agent (e.g. polio via GIT) to immunize other hosts, or revert the agent to virulent wild organism (e.g. BCG). D. These vaccines are heat labile (VS: killed vaccines are heat stable) and should be properly refrigerated to maintain effectiveness. E. Vaccines prepared in chick embryo may cause allergic reactions in persons allergic to eggs.

Note: MMR & DTP (Diphtheria, Tetanus & Pertussis) are widely used, and a proper immune response occurs to all antigens provided antigenic competition does not occur ( poor & strong antigens should be balanced).

3. Toxoids: These are vaccines prepared by detoxifying the toxins (e.g., by formaldehyde) of some bacteria. Examples: toxoid vaccines for diphtheria & tetanus. 4. Vaccines prepared from bacterial fractions or viral components: Examples; a. capsular polysaccharide vaccine of meningococci, pneumococci & H. influenzae. b. acellular vaccine of B. pertussis containing purified protein of m.o. c. purified surface antigen of hepatitis B virus. d. the split virus vaccine of influenza containing haemagglutinin & neuraminidase.

The capsular polysaccharide vaccines alone are poor immunogens (antigens) in children below 2 years of age. Example: H. influenzae b vaccine, but when conjugated to diphtheria toxoid or other carrier proteins its immunogenicity is enhanced. It produces anti-capsular opsonizing (IgG) antibodies. 5. Recombinant vaccines: Are prepared by recombinant DNA technology. Example: hepatitis B virus vaccine (good & safe).

Approaches to Develop New Vaccines: Advances in recombinant DNA technology, synthesis of peptides & bioengineering lead to the production of new vaccines: 1. Subunit vaccines: In which microbial polypepti- des are isolated (e.g. Hepatitis B, Influenza). 2. Recombinant antigen vaccines: In which antigens are synthesized by inserting the coding genes into E. coli or yeast cells (e.g. hepatitis B). 3. Recombinant avirulent vectors vaccines: In which the gene coding for the antigen is inserted into the genome of avirulent vector as vaccinia virus or others.

4. Synthetic peptides vaccines: It is now technically possible to synthesize short peptides that corres- pond to antigenic determinants on viral or bacterial protein to be used as vaccine (e.g. cholera toxin & polio v.). 5. Induction of attenuated non-reverting mutation: Genetic engineering techniques are used to attenuate a virus irreversibly by selectively removing genes of virulence

6. DNA vaccines: Plasmid vectors carrying microbial DNA encoding antigenic proteins is injected directly into the muscle of the recipient. The antigen is then expressed and stimulates both humoral and cellular immunity (e.g viral vaccine) 7. Mucosal vaccines (locally administered) Intranasally administered aerosol vaccines are developed, as viral respiratory disease and measles to stimulate local antibodies at the site of entry.

Characteristics of effective vaccines: Safety; no disease must be caused by the vaccine itself. Protection; the population must be protected (herd immunity). Long lasting effects; induce T- and B- cell memory. Cost; inexpensive. Administration; easy to deliver with no side-effects.

AGE VACCINE At birth – 1 month BCG 2 months DTP, OPV, HBV 4 months 6 months 9 months Measles 15 months MMR 18 months DTP, OPV 4-6 years 10 years Td

DTP : Diphtheria, Tetanus, Pertussis. Td : Tetanus, Diphtheria. MMR : Mumps, Measles, Rubella. BCG : Bacillus Calmette-Guerin (T.B.). OPV : Oral poliovirus vaccine. HBV : Hepatitis B vaccine. Note: 1. Hib (H. influenza b polysaccharide conjugate vaccine) and PCV ( Heptavalent Pneumococcal conjugate vaccine) can be given from 2 up to 15 months). 2. DTaP (Diphtheria, Tetanus, Acellular Pertussis) is preferable in some countries than DTP. 3. The American Academy of Pediatrics recommended (2003) to drop OPV and use Salk IPV (Inactivated Polio Vaccine) instead for ALL doses. 4. Varicella vaccine may used after 12 months of age for children lacking history of chicken pox. Also, Hepatitis A vaccine may be given after 2 Y