Viral vaccines Current Practices

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Viral vaccines Current Practices



2. WHAT ARE VIRUSES Viruses are intracellular parasites unable to survive withouta living host Non-living ?; do not follow Kochs Postulates They cannot reproduce or metabolize on their own becausethey lack the self-machinery to do so Obligatory replicateinside host cells using host metabolism A single infectious virus particle is termed a Virion that actsas the vehicle for transmission All viruses consist of either double- or single-stranded DNA or RNA that is linear or circular (orfragmented)DR.T.V.RAO MD 2 3. VIRUSES A virus is a submicroscopic obligate parasitic particle that infectscells in biological organisms . Viruses are non-living particles that can only replicate when an organism reproduces thevirulent RNA or DNA. Among other things, viruses do not move, metabolize, or decay on their own. Virusesare obligate intracellular parasites that lack the cellular machinery for self-reproduction. Viruses infect eukaryotes and prokaryotes such as bacteria; bacteriophages. Typically viruses carry a small amount of genetic material, either in the form ofRNA or DNA, but not both, surrounded by some form of protective coat consistingof proteins, lipids, glycoproteins or a combination. The viral genome codes for the proteins that constitute this protective coat, aswell as for those proteins required for viral reproduction that are not provided bythe host cell.DR.T.V.RAO MD3 4. HISTORICAL BEGINNINGSmallpox was the first disease people tried to prevent bypurposely inoculating themselves with other types of infections.Inoculation is believed to have started in India or China before200 BC. Physicians in China immunized patients by picking offpieces from drying pustules of a person suffering from a mildcase of smallpox, grinding the scales to a powderysubstance, and then inserting the powder into the persons nosein order for them to be immunized. In 1718, Lady Mary WortleyMontague reported that the Turks have a habit of deliberatelyinoculating themselves with fluid taken from mild cases ofsmallpox. Lady Montague inoculated her own children in thismannerDR.T.V.RAO MD 4 5. ORIGIN OF VACCINESIn 1796, during the heyday of the smallpox virus in Europe, an Englishcountry doctor, Edward Jenner, observed that milkmaids would sometimesbecome infected with cowpox through their interactions with dairy cowsudders. Cowpox is a mild relative of the deadly smallpox virus. Building onthe foundational practice of inoculation, Jenner took infectious fluid from thehand of milkmaid Sarah Nelmes. He inserted this fluid, by scratching orinjection, into the arm of a healthy local eight year old boy, James Phipps.Phipps then showed symptoms of cowpox infection. Forty-eight dayslater, after Phipps had fully recovered from cowpox, Jenner injected somesmallpox-infected matter into Phipps, but Phipps did not later show signs ofsmallpox infection DR.T.V.RAO MD 5 6. BASIC STRATEGIES IN VACCINATIONDR.T.V.RAO MD6 7. VACCINES [BACKGROUND] Vaccine comes from the Latin word vacca which pertains tocows Based on the practice of variolation which was inoculatinghealthy individuals with weak forms of smallpox 1st Vaccine (1796): Edward Jenner inoculated milkmaids withcowpox to confer protective immunity against smallpox. 1st Attenuated Vaccine (1885): Louis Pasteur developed avaccine to protect against rabies; vaccine is made from viablevirus with reduced virulence (lower degree of pathogenicity).DR.T.V.RAO MD7 8. VACCINES [BACKGROUND] Most damage to a cell is done too early before any clinicalsymptoms of disease appear. Treatment becomesdifficult, therefore, prevention is preferred over post-exposurevaccines. The Main Idea: Vaccines contain a weak form of a virus/microbethat is not pathogenic Vaccines are used to protect a large number of people fightagainst epidemics and pandemics. Good vaccines elicit a secondary immune response that willeliminate the pathogen.DR.T.V.RAO MD8 9. TIMELINE OF VACCINES 18th century 1796 First vaccine for smallpox, first vaccine for any disease 19th century 1882 First vaccine for rabies 20th century 1932 First vaccine for yellow fever 1945First vaccine for influenza 1952 First vaccine for polio 1954 First vaccine for Japanese encephalitis 1957 First vaccine for adenovirus-4 and 7DR.T.V.RAO MD9 10. TIMELINE OF VACCINES 1962 First oral polio vaccine 1964 First vaccine for measles 1967 First vaccine for mumps 1970 First vaccine for rubella 1974 First vaccine for chicken pox 1977 First vaccine for pneumonia 1978 First vaccine for meningitis 1981 First vaccine for hepatitis B 1992 First vaccine for hepatitis A 1998 First vaccine for rotavirusDR.T.V.RAO MD10 11. VACCINES BASICS The principle of vaccination is to induce a "primed" state in the vaccinated subject so that, followingexposure to a pathogen, a rapid secondary immune response is generated leading to the acceleratedelimination of the organism and protection from clinical disease. Success depends on the generation ofmemory T and B cells and the presence in the serum of neutralizing antibody. Attributes of a good vaccine 1.Ability to elicit the appropriate immune response for the particular pathogen: Tuberculosis - cell mediated response most bacterial and viral infections - antibody 2. Long term protection ideally life-long3. Safety vaccine itself should not cause disease4. Stable retain immunogenicity, despite adverse storage conditions prior to administration5. Inexpensive DR.T.V.RAO MD11 12. VACCINES IMITATE ANINFECTION Vaccines contain a weakened form of themicrobe that doesnt cause disease orreproduce Vaccines stimulate the macrophages, whichpresent the antigens to T and B cells The mock infection is rapidly cleared, and youare left with a supply of memory T cells and Bcells to protect you against of future infectionof this typeDR.T.V.RAO MD12 13. DR.T.V.RAO MD 13 14. DR.T.V.RAO MD 14 15. THE IMMUNE SYSTEM & RESPONSE AND VACCINES Once vaccinated, the immune system takes a week andupwards to begin fighting off the organism. Immunity is conferred once the immune system is trainedto resist a certain disease a vaccine is developed for Artificially Acquired Immunity is provided Childhood vaccinations are highly encouraged against: Measles, Mumps, Rubella, Polio, Hepatitis A &B, Diphtheria, Pertussis, Tetanus, ChickenPox, HIB, Rotavirus, Meningococcal disease, and Influenza.DR.T.V.RAO MD 15 16. THE IMMUNE SYSTEM & RESPONSE Macrophages: white blood cells that detect and engulf viralantigens; microbes are carried to lymphocytes Within lymph nodes, T and B cells are activated T cells: able to recognize virus infected cells early in infectionperiod and release cytotoxins to destroy them B cells: secrete antibodies that bind antigens on the virussurface. This coats the virus and prevents infection. B-cells canalso recognize virus infected cells late in infection Ideally, goodvaccines evoke both T and B cells Antibodies will activate macrophages to engulf viral antigensDR.T.V.RAO MD 16 17. VACCINE TYPESDR.T.V.RAO MD 17 18. LIVE (ATTENUATED) VACCINES Consist of a live form of the virus that has beenartificially weakened; select for mutants that will causewild-type infection without onset of disease Usually only takes 1 or 2 doses to confer life longimmunity (childhood vaccines). Must be careful of the small chance of reversion to amore virulent form Elicit good immune response, inexpensive, but must becautiously stored to maintain viabilityDR.T.V.RAO MD 18 19. INACTIVATED VACCINES Using heat, radiation or chemicals a virus is killed and is no longer infectious WHY USE AN INACTIVATED VIRUS? Attenuated strains have yet to be developed Reversion to virulent forms is a high occurrence Requires no refrigeration The downside is that the immunogenicity is lowered and multiple doses willbe required (i.e. booster shots) Adjuvants: administered simultaneously to enhance immune response Combination vaccines: DTP and MMR More expensive to prepareDR.T.V.RAO MD19 20. VACCINES IN GENERAL USEMeasles Live attenuated virus grown in chick embryofibroblasts, first introduced in the 1960s. Itsextensive use has led to the virtual eradication ofmeasles in the first world. In developedcountries, the vaccine is administered to all childrenin the second year of life (at about 15 months).However, in developing countries, where measles isstill widespread, children tend to become infectedearly (in the first year), which frequently results insevere disease. It is therefore important toadminister the vaccine as early as possible (betweensix months and a year). If the vaccine isadministered too early, however, there is a poor takerate due to the interference by maternal antibody.For this reason, when vaccine is administered beforethe age of one year, a booster dose is recommendedat 15 MDDR.T.V.RAO months. 20 21. VACCINES IN GENERAL USEMumps Live attenuated virus developed in the1960s. In first world countries it isadministered together with measles and rubellaat 15 months in the MMR vaccine. The current "Jeryl Lynn" strain of the mumpsvaccine was developed by Dr. Maurice Hillmanfrom the mumps virus that infected his 5-year-old daughter (whose name was Jeryl Lynn).This vaccine, combined with rubella or bothrubella and measles vaccines (MMR), hasbeen widely used worldwide (300 million dosesgiven) since it was approved by the FDA in1967.DR.T.V.RAO MD 21 22. VACCINES IN GENERAL USEPolio Two highly effective vaccines containing all 3 strains of poliovirus are ingeneral use: The killed virus vaccine (Salk, 1954) is used mainly inSweden, Finland, Holland and Iceland. The live attenuated oral polio vaccine (Sabin, 1957) has beenadopted in most parts of the world; its chief advantages being: lowcost, the fact that it induces mucosal immunity and the possibilitythat, in poorly immunized communities, vaccine strains might replacecirculating wild strains and improve herd immunity. Against this is therisk of reversion to virule