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clase de presicption y progamacion de vaccines faby bebe.pptx
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- 2. • It exploitsthe property of immunological memory to provide long- lasting protection against infectious disease. • e first deliberate scientific attempt to prevent an infectious disease and was based on the notion that infection with a mild disease (cowpox) might protect against infection with a similar but much more serious one (smallpox)
- 3. • Vaccination appliesimmunological principles to human health • Adaptive immunity and the ability of lymphocytes to develop memory for a pathogen's antigens underlie vaccination • from whole organisms to simple peptides and polysaccharides. • Adjuvants enhance antibody production, they concentrate antigen at appropriate sites or induce cytokines.
- 4. • Vaccine safetyis an overriding consideration. When immunization frequencies fall, the population as a whole is not protected. Fears over the safety of the MMR vaccine resulted in measles epidemics and increases in incidence of rubella. • Non-specific immunization, for example by cytokines, may be of use in selected conditions.
- 5. • In anyimmune response, antigens induce clonal expansion in specific T and/or B cells, leaving behind a population of memory cells. next encounter with the same antigen(s) to induce a secondary response, which is more rapid and effective than the normal primary response. • For many infections the primary response may be too slow to prevent serious disease, BUT if it´s been exposed to antigens from the organism in a vaccine before encountering the pathogen, the expanded population of memory cells and raised levels of specific antibody are able to protect against disease
- 6. Principles of vaccination •priming of specific lymphocytes to expand the pool of memory cells; • use of harmless forms of immunogen – attenuated organisms, subcellular fragments, toxoids or vectors; • use of adjuvants to enhance immune responses; and • production of safe, affordable vaccines to promote herd immunity.
- 7. Herd immunity Vaccines canprotect populations as well as individuals Vaccines protect individuals against disease and if there are sufficient immune individuals in a population, transmission of the infection is prevented. This is known as herd immuneity . in developing vaccination programmes is the rate of spread of disease. R0 , which indicates how many people (on average) will become infected by an initial infected person. he higher the value of R 0 , the greater the level of immunity required in the total population (herd immunity) to prevent the disease from spreading. This is referred to as the critical immunization threshold
- 8. The size ofthe population that must be immune to avoid outbreaks depend: • If the organism is highly infectious so that one individual can rapidly infect several non-immune individuals, as is the case for measles, a high proportion of the population must be immune to maintain herd immunity. • f the infection is less readily transmitted, immunity in a lower proportion of the population may be sufficient to prevent disease transmission.
- 9. Effective vaccines mustbe safe to administer, induce the correct type of immunity and be affordable by progress was much slower and fears over vaccine safety made development more lengthy and costly. However, the advent of recombinant DNA technology has led to a number of significant advances in the first decade of the 21st century and a number of new, safe and effective vaccines have come onto the market during this period the population at which they are aimed
- 10. • development ofan effective vaccine has remained elusive, in particular, parasitic diseases and HIV
- 11. Antigen preparations usedin vaccines • the more antigens of the microbe retained in the vaccine, the better, • living organisms tend to be more effective than killed organism • diseases where a toxin is responsible for the pathology – in this case the vaccine can be based on the toxin alone * Live vaccines can be natural or attenuated organisms
- 12. Attenuated live vaccines •the preferred strategy for vaccine development has been to attenuate a human pathogen, with the aim of diminishing its virulence while retaining the desired antigens. • Attenuated microorganisms are less able to cause disease in their natural host
- 13. • virulence ,which is the ability to replicate efficiently and to disseminate widely within the body. viruses contain virulence genes that mimic or interfere with cytokine and chemokine function
- 14. Killed vaccines • Killedvaccines are intact but non-living organisms • hese are gradually being replaced by attenuated or subunit vaccines. • killed vaccine, which is safer than the attenuated vaccine, even though it is less effective. relevant when the risk of contracting the disease is low in comparison with the risk of developing adverse reactions to the vaccine.
- 15. Inactivated toxins andtoxoids are the most successful bacterial vaccines • The most successful of all bacterial vaccines, tetanus and diphtheria, are based on inactivated exotoxins ( Table 17.4 ) and in principle the same approach can be used for several other infections.
- 16. Subunit vaccines andcarriers • Aside from the toxin-based vaccines, which are subunits of their respective microorganisms, a number of other vaccines are in use that use antigens either purified from microorganisms or produced by recombinant DNA technology • Acellular pertussis vaccine consisting of a small number of proteins purified from the bacterium has been available for some years now and has been shown to be effective, safer and less toxic than the killed (whole organism) vaccine
- 17. • for manytypes of bacteria, virulence is determined by the bacterial capsular polysaccharide, • A major advance in the efficacy of subunit vaccines has been obtained by conjugating the purified polysaccharides to carrier proteins such as tetanus or diphtheria toxoid • These protein carriers, recruit T h 2 cells and the conjugates induce IgG antibody responses and more effective long-lasting protection.
- 18. Conjugate meningitis vaccine startingwith H. influenzae type B (Hib) in the early 1990s, conjugate vaccines for N. meninigitidis strains A, C, Y and W-135 are also now in widespread usage. In the UK, until 1992 when the vaccine was introduced, Hib was the major cause of infantile meningitis leading to many hundreds of cases per year. The introduction of the vaccine led to a very rapid decline, making Hib meningitis a very rare occurrence The serogroup C meningococcal vaccine was first introduced in the UK in 1999 and has resulted in a reduction of > 80% in the incidence of infection
- 19. Antigens can beexpressed from vectors • HPV has been established as the causative agent in cervical carcinoma and over 70% of cases are accounted for by the serotypes 16 and 18. the viral surface protein L1. Aggregates of L1 spontaneously assemble into virus-like particles (VLP) that are highly immunogenic. contain no nucleic acid, the vaccine cannot lead to HPV infection and is very safe
- 20. • The useof recombinant DNA technology lends itself well to interfacing with bioinformatics-based methodologies to identify potential target antigens for immunization – called reverse vaccinology.
- 21. Adjuvants enhance antibodyproduction • The increasing use of purified or recombinant antigens has refocused attention on the requirement to boost immune responses through the use of adjuvants • The difficulty with adjuvants is that they mediate their effect through stimulating the inflammatory response, generally necessary to produce a good immune response to antigen. Unfortunately, the inflammatory response is often responsible for the side effects of immunization, such as pain and swelling at the injection site, and can lead to greater malaise, elevated temperature and/or flu-like symptoms. • Adjuvants concentrate antigen at appropriate sites or induce cytokines
- 22. • Aluminium-adjuvanted vaccineshave been suspected to be associated with a condition known as macrophagic myofasciitis (MFF)
- 23. Vaccine administration • Mostvaccines are delivered by injection • lternatives to needle delivery do exist, however, and can be beneficial for use in mass vaccination programmes and for improving compliance in those with needle phobia • jet injectors can deliver vaccine intramuscularly, as with a needle, but they can also be used for cutaneous delivery, which should help to reduce the discomfort and potential for distress in infants. • Cutaneous delivery is a highly effective method for vaccination; the skin harbours many Langerhans cells, which are very active in antigen presentation to T cells in lymph nodes, to which they migrate when activated by exposure to antigen. They also help to initiate an inflammatory response through release of cytokines and chemical mediators, all of which can potentiate the vaccine.
- 24. • Because mostorganisms enter via mucosal surfaces, mucosal immunization makes logical sense. live attenuated vaccines can be effective when delivered orally, most killed vaccines are not.
- 25. Vaccine efficacy andsafety
- 26. Passive immunization • Passiveimmunization can be life-saving. The direct administration of antibodies still has a role to play in certain circumstance: for example, when tetanus toxin is already in the circulation.