Vaccines

1. Prabin Shah BScMLT, MSc(Biochemistr y)

2. Contents History Introduction Immunity and its types Principal of vaccination Types Vaccination schedule Special vaccines Hazards of vaccination

3. First recorded attempt at immunization occurred in 6th century China. drying & grinding up smallpox scabs & blowing them with a straw into the nostrils of immuno-compromised family members. By the 10th century, this practice had changed to the deliberate inoculation of dried pus from the smallpox pustules of one patient into the arm of a healthy person,(variolation) This method was used in parts of the Far East for centuries before Lady Mary Montagu brought it to England in 1721 from Istanbul.

4. Eventually, rst really effective vaccine was developed by the English physician Edward Jenner in 1796. NOW while many advances have occurred in the last two centuries, science is poised for even more in the future. Today, researchers are working to improve existing vaccines and to search for vaccine to fight HIV/AIDS, cancer and other diseases.

5. Introduction Vaccines With the exception of safe water, no other modality, not even antibiotics, has had such a major effect on mortality reduction The term vaccine was coined by Louis Pasteur. The term vaccine was derived from vacca, meaning cow, since Edward Jenner used cowpox virus (Vaccinia) to prevent smallpox infection. A vaccine is an immuno-biological substance designed to produce specific protection against a given disease. A vaccine is antigenic but not pathogenic. Vaccines have profoundly reduced the prevalence and impact of many infectious diseases that were once common and often deadly.

6. Properties of an ideal vaccine (easy to define, difficult to achieve) 6 Give life long immunity Broadly protective against all variants of organism Prevent disease transmission Rapidly induce immunity Effective in all subjects (the old & very young) Transmit maternal protection to the foetus Require few immunisations to induce protection Not need to be administered by injection (oral, intranasal, transcutaneous) Stable, cheap & safe

7. Routes of administration Deep subcutaneous or intramuscular route (most vaccines) Oral route (sabine vaccine, oral BCG vaccine) Intradermal route (BCG vaccine) Scarification (small pox vaccine) Intranasal route (live attenuated influenza vaccine) Scheme of immunization Primary vaccination One dose vaccines (BCG, variola, measles, mumps, rubella, yellow fever) Multiple dose vaccines (polio, DPT, hepatitis B) Booster vaccination To maintain immunity level after it declines after some time has elapsed (DT, MMR).

8. Types of immunity Vaccination is artificially acquired active immunity

9. Primary response to a vaccine most current vaccines induce protective antibodies 9 Principle of vaccination

10. Secondary response to an infection primed by vaccine 10

11. Primary & secondary antibody responses vaccination & infection 11

12. Types of vaccines Live vaccines Attenuated live vaccines Inactivated (killed vaccines) Subunit vaccines Conjugate vaccines Surface antigen (recombinant) vaccines. DNA vaccine Anti-idotypic vaccine

13. Live vaccine Live vaccines are made from live infectious agents without any amendment or changes. The only live vaccine is Variola small pox vaccine, made of live vaccinia cow-pox virus (not variola virus) which is not pathogenic but antigenic, giving cross immunity for variola. Live Attenuated Vaccines Virulent pathogenic organisms are treated to become attenuated and avirulent but antigenic. They have lost their capacity to induce disease but retain their immunogenicity. These vaccines may be given by injection or by the oral route.

14. Growing in foreign host in condition that makes its a virulent Administration orally, intradermal, intranasal, subcutaneous Examples: Vibrio ,Salmonella , BCG, Polio, JE, Yellow Fever Influenza , MMR, Chicken pox, Small pox

15. Advantages stimulate generation of cellular as well as humoral immune responses. Since these can multiply in the host, single administration of vaccine produce long-lived immunity. Multiple booster doses may not be required Oral preparations are less expensive than giving injections. elimination of wild type virus from the community Disadvantages May very rarely convert to its virulent form and cause disease. Live vaccines cannot be given to immuno-suppressed individuals,can cause serious illness or death in the vaccine recipient. Since they are live and because their activity depends on their viability, proper storage is critical.

16. Killed Vaccines When it is unsafe to use live microorganisms to prepare vaccines, they are killed or inactivated. Organisms are killed or inactivated by treatment with using heat, formaldehyde or gamma irradiation so that they cannot replicate at all, but remain antigenic. usually safe but less effective than live attenuated vaccines. route of administration Intramuscular(IM), Sub- cutaneous(SC) Examples: Salmonella typhi, Vibrio cholerae, Yersinia pestis, Bordetella pertussis, Poliomyelitis Salk, JE virus, Rabies virus, Influenza virus, Hepatitis A

17. Advantages Safe to use and can be given to immuno-deficient and pregnant individuals. Cheaper than live attenuated vaccine Storage not as critical as live vaccine Disadvantages microorganisms cannot multiply so periodic boosters must be given to maintain immunity. Only humoral immunity can be induced. Most killed vaccines have to be injected. Some vaccines such as Bordetella pertussis induce ill effects like post-vaccinial encephalomyelitis. Inactivation, such as by formaldehyde in the case of the Salk vaccine, may alter antigenicity.

18. Subunit vaccines Subunit vaccines contain purified antigens instead of whole organisms. Such a preparation consists of only those antigens that elicit protective immunity. Subunit vaccines are composed of toxoids, subcellular fragments, or surface antigens The effectiveness of subunit vaccines in increased by giving them in adjuvants. Route of administration Intramuscular Examples: Cell wall polysaccharide (Hemophilus influenzae,Nesseria meningitides, Streptococcus pneumoniae, Group B Streptococcus ,Salmonella typhi) Toxoid (Tetanus, Diphtheria) Membrane proteins (Influenza virus, HepatitisB)

19. Advantages can safely be given to immuno-suppressed people less likely to induce side effects. Disadvantages Antigens may not retain their native conformation, so that antibodies produced against the subunit may not recognize the same protein on the pathogen surface. Isolated protein does not stimulate the immune system as well as a whole organism vaccine.

20. Conjugate vaccines is a type of vaccine that is created by joining an antigen to a protein molecule. usually used to immunize babies and children against bacteria that have polysaccharide capsular The immature immune systems of very young people often have difficulty recognizing certain antigens, so ordinary vaccines may not be effective for some diseases. A conjugate vaccine, therefore, usually consists of a polysaccharide antigen combined with a carrier protein. The combination of the antigen with the protein creates a substance that is more easily recognizable to the white blood cells in the human blood, resulting in a stronger immune response. Examples: Tetramune vaccine,which combines the tetanus and diphtheria toxoids, whole-cell pertussis vaccine, and H. influenzae type b conjugate vaccine.

21. Recombinant vaccine The vaccines are produced using recombinant DNA technology or genetic engineering. Recombinant vaccines are those in which genes for desired antigens of a microbe are inserted into a vector. Examples: Hepatitis B, Diptheria, Cholera, Tetanus,

22. Advantages Those vectors that are not only safe but also easy to grow and store can be chosen. Antigens which may cause damaging responses can be eliminated from the vaccine. Example Cholera toxin A can be safely removed from cholera toxin. Disadvantages Since the genes for the desired antigens must be located, cloned, and expressed efficiently in the new vector, the cost of production is high. When engineered vaccinia virus is used to vaccinate, care must be taken to spare immunodeficient individuals.

23. DNA Vaccines DNA vaccines are being hailed as the most promising of all of the newer approaches to immunization. These vaccines are still in experimental stage. Like recombinant vaccines, genes for the desired antigens are located and cloned. DNA vaccines have induced both humoral and cellular immunity. Route of administration gene gun method, intradermal, get injection Examples: bird flu DNA vaccine

24. Advantages DNA is very stable,hence storage and transport are easy. DNA sequence can be changed easily in the laboratory. Inserted DNA does not replicate and encodes only the proteins of interest. Disadvantages Induction of autoimmune responses: anti-DNA antibodies may be produced against introduced DNA. Induction of immunologic tolerance: The expression of the antigen in the host may lead to specific non-responsiveness to that antigen.

25. Anti-idiotypic vaccine This unique amino acid structure in the antibody is known as the idiotype, which can be considered as a mirror of the epitope in the antigen. Antibodies can be raised against the idiotype by injecting the antibody into another animal. This anti-idiotype antibody mimics part of the three dimensional structure of the antigen. This can be used as a vaccine. When the anti-idiotype antibody is injected into a vaccine, antibodies (anti-idiotype antibodies) are formed that recognize a a structure similar to part of the virus and might potentially neutralize the virus. Advantage: Antibodies against potentially significant antigen can be produced. Disadvantage: Only humoral immunity is produced. There is no cellular immunity and poor memory. Identification and preparatistructure similar to part of the virus and might potentially neutralize the virus.

26. Advantage Antibodies against potentially significant antigen can be produced. Disadvantage Only humoral immunity is produced. There is no cellular immunity and poor memory. Identification and preparation of idiotypes is labor intensive and difficult.

27. Vaccination of those at occupational risks Depending upon the organisms they are exposed to vaccination can be done Occupation Vaccines Laboratory personals Q fever Australian bat lyssavirus (ABL) and rabies Anthrax Vaccinia poxviruses Poliomyelitis Typhoid, Yellow fever Meningococcal disease MMR Japanese encephalitis HepatitisB

28. Vaccination for travellers Varies according to the country of arrival and departure. Common vaccines according to the country traveled to: TAB, YF, cholera, meningiococcal, pneuomococcal, HIB, influenza, rabies, plague, Japanese encephalitis, tickborn encephalities, measles, Hepatitis B, Hepatitis A, Tetanus, poliomyletis,Typhoid, Hajj for instance necessates meningococcal vaccination from all over Yellow Fever from places like south Africa, and cholera from places like India. Vaccines against bioterrorism Anthrax Small pox Plague

29. Hazards of Immunization No immune response is entirely free from the risk of adverse reactions or remote squeal. The adverse reactions that may occur may be grouped under the following heads: Reactions inherent to inoculation Reactions due to faulty techniques Reactions due to hypersensitivity Neurological involvement Provocative reactions Others

30. Still more to done Around 24 million children under one year old almost 20% of the children born every year are not being reached with vaccines.

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