Transcript 12Immuniz
IMMUNIZATION 1 IMMUNIZATION • Immunization is a means of providing specific protection against many common and damaging pathogens by stimulating an organism's immune system. 2 Milestones in immunization 3000BC Evidence of sniffing powdered small pox crust in Egypt 2000BC Sniffing of small pox crust in China 1500BC Turks introduce variolation 1700AD Introduction of variolation in England and later in the US 3 Modern era of the vaccine 1885 Rabies vaccine (Pasteur) 1920s Diphtheria and Tetanus 1934 Pertussis 1955 Salk polio 4 Modern era of the vaccine 1960s 1985 Mumps measles and rubella virus Sabin polio Haemophilus 1990s Hepatitis and varicella 5 Pre- & post-vaccine incidence of common preventable diseases 6 Different modes of acquiring immunity Immunity Natural Acquired Passive Active Passive Igs IgG Infection Active Vaccination 7 Passive Immunity Natura l Artificia l Placental transfer of IgG Antibodies or immunoglobulins Colostral transfer of IgA Immune cells 8 Passive Immunization disease antibody source indication diphtheria, tetanus human, horse prophylaxis, therapy vericella zoster human immunodeficiencies gas gangrene, botulism, snake bite, scorpion sting horse post-exposure rabies, human post-exposure hypogammaglobulinemia human prophylaxis 9 Advantages and Disadvantages of Passive Immunization Advantages Disadvantages no long term protection immediate protection serum sickness risk of hepatitis and Aids graft vs. host disease (cell graft only) 10 Active Immunization Natural Artificial Attenuated organisms killed organisms exposure to subclinical infections sub-cellular fragments toxins others 11 Types of vaccines • Killed vaccines: These are preparations of the normal (wild type) infectious, pathogenic MO that has been rendered nonpathogenic, usually by chemical treatment such as with formalin that cross-links viral proteins. • Attenuated vaccines: These are live MO particles that grow in the vaccine recipient but do not cause disease because the vaccine virus has been altered (mutated) to a non-pathogenic form; for example, its tropism has been altered so that it no longer grows at a site that can cause disease. • Sub-unit vaccines: These are purified components of the MO, such as a surface antigen. • DNA vaccines: These are usually harmless MO into which a gene for a (supposedly) protective antigen has been spliced. The protective antigen is then made in the vaccine recipient to elicit an immune response 12 Advantages of attenuated vaccines 1. They activate all phases of immune system. They elicit humoral IgG and local IgA (figure 8) 2. They raise an immune response to all protective antigens. Inactivation, such as by formaldehyde in the case of the Salk vaccine, may alter antigenicity 3. They offer more durable immunity and are more crossreactive. Thus, they stimulate antibodies against multiple epitopes which are similar to those elicited by the wild type virus 4. They cost less to produce 5. They give quick immunity in majority of vaccinees 6. In the cases of polio and adenovirus vaccines, administration is easy 7. These vaccines are easily transported in the field 8. They can lead to elimination of wild type virus from the community 13 Disadvantages of Attenuated vaccine 1. Mutation. This may lead to reversion to virulence (this is a major disadvantage) 2. Spread to contacts of the vaccinee who have not consented to be vaccinated (This could also be an advantage in communities where vaccination is not 100%) 3. Spread of the vaccine virus that is not standardized and may be mutated 4. Sometimes there is poor "take" in tropics 5. Live viruses are a problem in immunodeficiency disease patients 14 Advantages of inactivated (Killed) vaccine 1. They give sufficient humoral immunity if boosters given 2. There is no mutation or reversion (This is a big advantage) 3. They can be used with immuno-deficient patients 4. Sometimes they perform better in tropical areas 15 Disadvantages of inactivated (Killed) vaccines 1. Some vaccinees do not raise immunity 2. Boosters tend to be needed 3. There us little mucosal / local immunity (IgA). This is important (figure 8) 4. Higher cost 5. In the case of polio, there is a shortage of monkeys 6. In the case of smallpox, there have been failures in inactivation leading to immunization with virulent virus. 16 Live Attenuated Vaccines Polio (Oral) Sabin not used in std. schedule measles, mumps & rubella Varicella zoster hepatitis A not required in SC yellow fever Military and travelers tuberculosis children with no history of chicken pox 17 Killed Whole-Organism Vaccines Polio Salk IM influenza Q fever population at risk typhoid, cholera, plague elderly and at risk epidemics and travelers rabies pertussis post exposure replaced by the acellular vaccine 18 Microbial Fragment Vaccines Bordetella. Pertussis virulence factor protein Haemophilus influenzae B protein conjugated polysaccharide Streptococcus pneumoniae Polysaccharide mixture Neisseria meningitidis polysaccharide 19 Microbial Fragment Vaccines Clostridium tetani (tetanus) inactivated toxin (toxoid) Corynebacterium diphtheriae inactivated toxin (toxoid) Vibrio cholerae toxin subunits Hepatitis B virus cloned in yeast 20 Modification of Toxin to Toxoid Toxin Toxoid chemical modification toxin moiety antigenic determinants 21 Future Vaccines 22 NEW METHODS OF VACCINE PRODUCTION 1. 2. 3. 4. Selection for mis-sense Synthetic peptides Anti-idiotype vaccines Recombinant DNA techniques 23 Selection for mis-sense Conditional lethal mutants. Temperature-sensitive mutants in influenza A and RSV have been made by mutation with 5-fluorouracil and then selected for temperature sensitivity. In the case of influenza, the temperature-sensitive gene can be reassorted in the laboratory to yield a virus strain with the coat of the strains circulating in the population and the inner proteins of the attenuated strain. Cold adapted mutants can also be produced in this way. It has been possible to obtain mis-sense mutations in all six genes for non-surface proteins. 24 Synthetic peptides Injected peptides which are much smaller than the original virus protein raise an IgG response but there is a problem with poor antigenicity. This is because the epitope may depend on the conformation of the virus as a whole. A non-viral example that has achieved some limited success is a prototype anti-malarial vaccine. 25 Anti-idiotype vaccines An antigen binding site in an antibody is a reflection of the three-dimensional structure of part of the antigen, that is of a particular epitope. This unique amino acid structure in the antibody is known as the idiotype which can be thought of as a mirror of the epitope in the antigen. Antibodies (anti-ids) can be raised against the idiotype by injecting the antibody into another animal. This gives us an anti-idiotype antibody and this, therefore, mimics part of the three dimensional structure of the antigen, that is, the epitope. This can be used as a vaccine. When the antiidiotype antibody is injected into a vaccinee, antibodies (anti-anti-idiotype antiobodies) are formed that recognize a structure similar to part of the virus and might potentially neutralize the virus. This happens: Anti-ids raised against antibodies to hepatitis B S antigen elicit anti-viral antibodies. 26 27 Recombinant DNA techniques 1. Attenuation of virus 2. Single gene approach (Yeast) 3. Cloning of a gene into another virus 28 DNA VACCINES • These vaccines are based on the deliberate introduction of a DNA plasmid into the vaccinee. The plasmid carries a protein-coding gene that transfects cells in vivo at very low efficiency and expresses an antigen that causes an immune response. 29 Advantages of DNA vaccines 1. Plasmids are easily manufactured in large amounts 2. DNA is very stable 3. DNA resists temperature extremes and so storage and transport are straight forward 4. A DNA sequence can be changed easily in the laboratory. This means that we can respond to changes in the infectious agent 5. By using the plasmid in the vaccinee to code for antigen synthesis, the antigenic protein(s) that are produced are processed (post-translationally modified) in the same way as the proteins of the virus against which protection is to be produced. This makes a far better antigen than, for example, using a recombinant plasmid to produce an antigen in yeast (e.g. the HBV vaccine), purifying that protein and using it as an immunogen. 6. Mixtures of plasmids could be used that encode many protein fragments from a virus or viruses so that a broad spectrum vaccine could be produced 7. The plasmid does not replicate and encodes only the proteins of interest 8. There is no protein component and so there will be no immune response against the vector itself 9. Because of the way the antigen is presented, there is a cell-mediated response that may be directed against any antigen in the pathogen. This also offers protection against diseases caused by certain obligate intracellular pathogens (e.g. Mycobacterium tuberculosis) 30 Possible Problems of DNA vaccines 1. Potential integration of plasmid into host genome leading to insertional mutagenesis 2. Induction of autoimmune responses (e.g. pathogenic anti-DNA antibodies) 3. Induction of immunologic tolerance (e.g. where the expression of the antigen in the host may lead to specific nonresponsiveness to that antigen) 31 Problems in vaccine development • Different types of virus may cause similar diseases -- e.g. the common cold. As a result, a single vaccine will not be possible against such a disease • Antigenic drift and shift -- This is especially true of RNA viruses and those with segmented genomes • Large animal reservoirs. If these occur, re-infection after elimination from the human population may occur • Integration of viral DNA. Vaccines will not work on latent virions unless they express antigens on cell surface. In addition, if the vaccine virus integrates into host cell chromosomes, it may cause problems (This is, for example, a problem with the possible use of anti-HIV vaccines based on attenuated virus strains) • Transmission from cell to cell via syncytia - This is a problem for potential AIDS vaccines since the virus may spread from cell to cell without the virus entering the circulation. • Recombination and mutation of the vaccine virus in an32 attenuated vaccine. The eradication of smallpox • There is no animal reservoir for variola, only humans are infected by this virus • Once a person has been infected by the virus, there is lifelong immunity, although this may not be the case with people immunized using the vaccine strain • Subclinical cases rare and so an infected person can be identified and isolated • Infectivity does not precede overt symptoms, that is there is no prodromal phase • There is only one Variola serotype and so the vaccine is effective against all virus strains • The vaccine is very effective • There has been a major commitment by the World 33 Health Organization and governments Vaccination checklist Here's a checklist of the vaccines that are routinely offered to everyone in the UK for free on the NHS, and the age at which you should ideally have them. 2 months: Diphtheria, tetanus, pertussis (whooping cough), polio and Haemophilus influenzae type b (Hib, a bacterial infection that can cause severe pneumonia or meningitis in young children) given as a 5-in-1 single jab known as DTaP/IPV/Hib Pneumococcal infection 34 جدول التطعيمات األساسية الزيارة الوالدة شهرين شهور 4 شهور 6 شهور 9 شهر 12 شهر 18 شهر 24 سنوات 4-6 35 اللقاح Basic Vaccination Schedule Vaccine Vaccination checklist الدرن BCG اإللتهاب الكبدي (ب) HepB شلل األطفال المعطل IPV )الثالثي البكتيري ؛ اإللتهاب الكبدي (ب) ؛ المستدمية النزلية( ) ( DTP , HepB شلل األطفال الفموي OPV )الثالثي البكتيري ؛ اإللتهاب الكبدي (ب) ؛ المستدمية النزلية( )(DRP , HepB , Hib شلل األطفال الفموي OPV )الثالثي البكتيري ؛ اإللتهاب الكبدي (ب) ؛ المستدمية النزلية( )(DRP , HepB , Hib الحصبة المفرد )Measles (mono شلل األطفال الفموي OPV الثالثي الفيروسي MMR الجديري المائي Varicella شلل األطفال الفموي OPV )الثالثي البكتيري ؛ المستدمية النزلية( ) ( DTP m HibH influenzae type B اإللتهاب الكبدي (أ) ) Hepatitis ( A اإللتهاب الكبدي (أ) ) Hepatitis ( A شلل األطفال الفموي OPV الثالثي البكتيري DTP الثالثي الفيروسي +الجديري المائي MMR, Varicella Visit At Birth 2 months 4 months 6 months 9 months 12 months 18 months 24 months 4-6 years Adverse Events Occurring Within 48 Hours DTP of Vaccination Event local redness, swelling, pain systemic: Mild/moderate fever, drowsiness, fretfulness vomiting anorexia systemic: more serious persistent crying, fever collapse, convulsions acute encephalopathy permanent neurological deficit 36