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Vaccines are important in human health and disease, More understanding is needed to explore the implications and limitations of newer generation of clinical practice

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  1. 1. Newer Vaccines for Clinical Use Dr.T.V.Rao MD
  2. 2. What is a “ Vaccine” <ul><li>The term vaccine derives from Edward Jenner's 1796 use of the term cow pox (Latin) variola vaccinæ , adapted from the Latin vaccīn-us , from vacca cow), which, when administered to humans, provided them protection against smallpox </li></ul>
  3. 3. Vaccine- Definition <ul><li>A vaccine is any preparation intended to produce immunity to a disease by stimulating the production of antibodies. Vaccines include, for example, suspensions of killed or attenuated microorganisms, or products or derivatives of microorganisms. The most common method of administering vaccines is by injection, but some are given by mouth or nasal spray. </li></ul>
  5. 5. Historical Picture of Vaccination
  6. 6. Vaccine stimulates Immune System <ul><li>A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe. The agent stimulates the body's immune system to recognize the agent as foreign, destroy it, and &quot;remember&quot; it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters </li></ul>
  7. 7. Preparation of Vaccines <ul><li>a. Live attenuated organisms which have been passed repeatedly in tissue culture or chick embryos so that they have lost their capacity to cause disease, but retained an ability to induce antibody response, such as polio (Sabin), measles, rubella, mumps, yellow fever, BCG, typhoid and plague. </li></ul><ul><li>b. Inactivated or killed organisms which have been killed by heat or chemicals but retain and ability to induce antibody response. They are generally safe but less efficacious than live vaccines and require multiple doses; e.g. polio (Salk), influenza, rabies and Japanese encephalitis. </li></ul>
  8. 8. Preparation of Vaccines <ul><li>c. Cellular fractions : usually polysaccharide fraction of the cell wall of a disease causing organism, such as pneumococcal pneumonia or meningococcal meningitis </li></ul><ul><li>d. Recombinant vaccines : produced by methods in which specific DNA sequences are inserted by molecular engineering techniques, e.g. DNA sequences spliced to vaccinia virus grown in cell culture to produces an effective influenza vaccine, and Hepatitis B vaccine by similar methods. </li></ul>
  9. 9. Passive Immunity “Vaccination ” <ul><li>Toxoids or antisera : are modified toxins made non-toxic to stimulate formation of an antitoxin, such as those produced to protect against toxins of tetanus, diphtheria, botulism, gas gangrene, snake and scorpion venom. </li></ul><ul><li>  </li></ul><ul><li>Immune globulin : An antibody containing solution derived from human blood in the form of pooled plasma, used primarily for immunity for passive immunization such as for immuno-compromised persons e.g. smallpox response groups. </li></ul><ul><li>  </li></ul><ul><li>Antitoxin : is an antibody derived from serum of animals after stimulation with specific antigens and used to provide passive immunity in humans. </li></ul><ul><li>  </li></ul>
  10. 10. Life cycle of Vaccination
  11. 11. Timeline of Vaccines <ul><li>18th century </li></ul><ul><li>1796 First vaccine for smallpox , first vaccine for any disease </li></ul><ul><li>19th century </li></ul><ul><li>1882 First vaccine for rabies </li></ul>
  12. 12. Timeline of Vaccines <ul><li>20th century </li></ul><ul><li>1932 First vaccine for yellow fever </li></ul><ul><li>1945 First vaccine for influenza </li></ul><ul><li>1952 First vaccine for polio </li></ul><ul><li>1954 First vaccine for Japanese encephalitis </li></ul><ul><li>1957 First vaccine for adenovirus -4 and 7 </li></ul><ul><li>1962 First oral polio vaccine </li></ul><ul><li>1964 First vaccine for measles </li></ul><ul><li>1967 First vaccine for mumps </li></ul>
  13. 13. Timeline of Vaccines <ul><li>1970 First vaccine for rubella </li></ul><ul><li>1974 First vaccine for chicken pox </li></ul><ul><li>1977 First vaccine for pneumonia </li></ul><ul><li>1978 First vaccine for meningitis </li></ul><ul><li>1981 First vaccine for hepatitis B </li></ul><ul><li>1992 First vaccine for hepatitis A </li></ul><ul><li>1998 First vaccine for rotavirus </li></ul>
  14. 14. World Health Organisation Reports <ul><li>&quot;Nearly nine million children under 14 years of age die every year from infectious disease. And at least a third of them could be saved if existing vaccines were more widely used, but the rest only if suitable new vaccines were developed ...&quot; </li></ul>
  15. 15. Vaccines use in the world <ul><li>For the past two decades, in most developing countries, vaccination restricted only to the initial EPI vaccines </li></ul><ul><li>Where-as in most developed countries, several new vaccines such as Hep B, Hib, meningococcal, pneumococcal, were gradually added to the initial EPI vaccines, </li></ul><ul><li>Thus widening the gap in protection against infectious diseases between the rich and the poor </li></ul>
  16. 16. Number of Childhood Vaccines Routinely Used in Developing and Established Market Countries Varicella Acell pertussis Pneumococcal * meningoccoal C* Measles DPT Poliomyelitis BCG Hepatitis B** Measles Mumps Rubella DPT Poliomyelitis Haemophilus Influenzae Hepatitis B *Estimated future use **Used in ~ 50% of global birth cohort
  17. 17. Newer Vaccines
  18. 18. Stages of Review and Regulation for Devloping Vaccines <ul><li>Phase 1 - Safety, immunogenicity (prelim) </li></ul><ul><li>Phase 2 – Immunogenicity, Safety, Dose Ranging </li></ul><ul><li>Phase 3 – Efficacy, Safety, Immunogenicity </li></ul><ul><li>BLA – Pre-clinical and clinical data to support approval, inspection </li></ul><ul><li>Phase 4 – Inspection, Safety, Efficacy, Lot Release </li></ul><ul><li>BLA-Supplement (post-approval changes) </li></ul>
  19. 19. Stages of Vaccine Development <ul><li>Vaccine development proceeds through discovery, process engineering, toxicology and animal studies to human Phase I, II, and III trials. The process can take more than 10 years, depending on the disease. </li></ul>
  20. 20. Stage I Development <ul><li>The human trials focus initially on safety, involving small groups of people </li></ul>
  21. 21. Stage II of Development <ul><li>Progress to moderate-sized &quot;target&quot; populations (persons close to the age and other characteristics for whom the vaccine is intended) to determine both safety and the stimulation of immune response. </li></ul>
  22. 22. Stage III of Development <ul><li>Finally to large target populations to establish whether a vaccine actually prevents a disease as intended (efficacy) </li></ul>
  23. 23. An ideal Vaccine should be …. <ul><li>Good immune response </li></ul><ul><li>Both Cell Mediated Immunity and antibody responses. </li></ul><ul><li>Immunity is long lived </li></ul><ul><li>Single dose </li></ul><ul><li>Safety </li></ul><ul><li>Danger of reversion to virulence, or Severe disease in immunocomprised </li></ul><ul><li>Stability </li></ul><ul><li>Organisms in the vaccine must remain viable in order to infect and replicate in the host </li></ul><ul><li>Vaccine preparations are therefore very sensitive to adverse storage conditions </li></ul><ul><li>Maintenance of the cold chain is very important. </li></ul><ul><li>Expense </li></ul><ul><li>Cheap to prepare </li></ul>
  24. 24. Causes of death in children less than 5 years old 19% 20% 20% 13% The Global Burden of Disease Murray and Lopez, editors Total - 12.8 million
  25. 26. New approved vaccines <ul><li>A number of new vaccines with major potential for controlling infectious diseases have just been licensed or are at advanced stages of development. Among the illnesses targeted are rotavirus diarrhoea, pneumococcal disease, and cervical cancer (as caused by human papillomavirus), which together kill more than a million people each year, most of them in developing countries. </li></ul>
  26. 27. Bacterial Meningitis kills several in Developing world <ul><li>Haemophilus influenzae type b (Hib) </li></ul><ul><ul><li>30% -50% of bacterial meningitis </li></ul></ul><ul><li>Pneumococcus </li></ul><ul><ul><li>25- 35% of bacterial meningitis </li></ul></ul><ul><li>Meningococcus </li></ul><ul><ul><li>25 - 35% of bacterial meningitis (except during epidemics) </li></ul></ul>
  27. 29. Meningococcal Meningtis Threat to AFRICA <ul><li>The African &quot;meningitis belt&quot; - which includes all or part of 21 countries stretching south of the Sahara desert from Senegal to Ethiopia - is the site of frequent epidemics, usually caused by serogroup A meningitis. Over the past decade more than 700 000 cases have been reported. Roughly 10-20 % of persons infected die, and one out of five survivors is likely to suffer from a permanent disability such as hearing loss, mental retardation, or paralysis. </li></ul>
  28. 30. Status of vaccine development <ul><li>Polysaccharide vaccines (vaccines made from complex sugars taken from the outer coats of the Men bacterium) are currently in use, but are not very effective at protecting young children, do not create long-lasting immunity, and do not confer a &quot;herd effect&quot;. Because of these shortcomings, immunization with polysaccharide vaccines is usually undertaken only after the onset of an epidemic. </li></ul>
  29. 31. Rotavirus Diarrhoeas <ul><li>Acute diarrhoea is responsible for nearly 1.9 million deaths per year in children under age five. Rotavirus is responsible for as much as one fourth of these casualties, almost all of which occur in developing countries. </li></ul>
  30. 33. Global Density of Rota viral Infections
  31. 34. Status of vaccine development: <ul><li>RotaRix, a vaccine developed by GlaxoSmithKline (GSK), against rotavirus diarrhoea is now licensed in many countries. In addition to being available on the private market in these countries, it has now been introduced in the public sector immunization programmes of Brazil, El Salvador, Mexico, Panama and Venezuela. . A Phase III trial is also under way in South Africa and Malawi. </li></ul>
  32. 35. Merck & Co.’s RotaTeq <ul><li>RotaTeq, introduced in 2006 for kids aged 2 months, 4 months, and 6 months, is a highly promising protection against the highly contagious disease –Rotavirus, says CDC. </li></ul><ul><li>The Centers for Disease Control and Prevention (CDC) believes that the level of protection provided by the vaccine is much stronger than they originally anticipate </li></ul>
  33. 36. Pneumococcal disease and Vaccination <ul><li>Acute lower respiratory infections are responsible for close to two million deaths per year and a large proportion of these are caused by Streptococcus pneumoniae (pneumococcus). </li></ul>
  34. 37. Prevenar contain seven serotypes <ul><li>A seven-valent conjugate vaccine called Prevnar (or Prevenar) is designed to act against seven strains of pneumococcal disease. It has been developed by Wyeth Vaccines and is licensed in the United States and over 70 other countries, but does not include two serotypes (types 1 and 5) that cause a high percentage of pneumococcal illness in developing countries. ( </li></ul>
  35. 38. Nine-valent conjugate vaccine a Succesul trial in Gambia <ul><li>Wyeth Vaccines has also completed evaluation of a nine-valent conjugate vaccine, including serotypes 1 and 5. A Phase III trial of the vaccine involving 40 000 people was completed in South Africa in 2002, and a Phase III trial with 17 437 subjects was concluded in the Gambia in 2004. </li></ul>
  36. 39. Challenges to identify Pneumococcal infections <ul><li>It can be difficult to establish the extent of pneumococcal disease as developing countries often lack the laboratory facilities, expertise, and resources to do so. As a result, public health decision-makers are often unaware of the prevalence of the disease and of the toll it exacts in death and disability. Because of the scarcity of data from developing countries, there is concern over the appropriate serotype valence for developing countries </li></ul>
  37. 40. Human papillomavirus (HPV) <ul><li>Sexually transmitted HPV is the major cause of cervical cancer, the most common cause of cancer deaths among women in developing countries. About 5,00 000 cases occur each year, 80% of them in developing countries. Cervical cancer kills some 240 000 women annually. </li></ul>
  38. 41. HPV 16 and 18 major types causing Carcinoma cervix <ul><li>HPV types 16 and 18 cause around 70% of HPV cervical cancers globally, but the vaccines in development will not cover the 30% of cancers attributed to other HPV types. Because these other types are numerous and individually only contribute a small percentage, significantly expanding vaccine coverage against them may present technical challenges for manufacturers. </li></ul>
  39. 42. Two types of vaccines for Human Papilloma virus prevention <ul><li>Bivalent human papillomavirus vaccine (HPV2) licensed for use in females </li></ul><ul><li>Either HPV2 or quadrivalent HPV vaccine (HPV4) used for females ages 19-26 years </li></ul><ul><li>Quadrivalent human papillomavirus vaccine (HPV4) licensed for use in males </li></ul><ul><ul><li>HPV4 may be administered to males aged 9 through 26 years to reduce their likelihood of acquiring genital warts. </li></ul></ul>
  40. 43. GARDASIL <ul><li>Gardasil, an HPV vaccine recently licensed by Merck, covers four types of HPV, including the cancer-causing types 16 and 18 and types 6 and 11 for non-cancerous genital warts. A second vaccine, developed by GSK, covers HPV types 16 and 18 alone </li></ul>
  41. 44. GARDASIL <ul><li>GARDASIL is the only human papillomavirus (HPV) vaccine that helps protect against 4 types of HPV. In girls and young women ages 9 to 26, GARDASIL helps protect against 2 types of HPV that cause about 75% of cervical cancer cases, and 2 more types that cause 90% of genital warts cases. In boys and young men ages 9 to 26, GARDASIL helps protect against 90% of genital warts cases. </li></ul>
  42. 45. How long vaccination is effective and Ideal age for Vaccination <ul><li>The duration of the immunity conferred by the vaccines is not yet known, and only time and follow up studies will provide this critical information... Because HPV is spread by sexual contact, and the high-risk years for infection are roughly from ages 18 to 25, the best subjects for vaccination will likely be pre-adolescents or adolescents, unlike for traditional vaccination programmes, which are aimed mostly at infants and pregnant women. </li></ul>
  43. 46. FDA approves Gardasil <ul><li>In October 2009, the FDA approved the use of GARDASIL in boys and young men ages 9 to 26 to protect against 90% of genital warts cases. </li></ul>
  44. 47. Meningococcal meningitis A Vaccine (Men A) <ul><li>Polysaccharide vaccines (vaccines made from complex sugars taken from the outer coats of the Men bacterium) are currently in use, but are not very effective at protecting young children, do not create long-lasting immunity, and do not confer a &quot;herd effect&quot; - that is, do not prevent spread of the disease in non-vaccinated people through reduction of the carriage of the infectious agent by vaccinated people during epidemics </li></ul><ul><li>Because of these shortcomings, immunization with polysaccharide vaccines is usually undertaken only after the onset of an epidemic. </li></ul>
  45. 48. Better Vaccine for Meningococcal Infection <ul><li>To provide greater and more efficient protection, a public-private effort called the Meningitis Vaccine Project (MVP) is developing a Men A conjugate vaccine. This vaccine is intended to have long-lasting effect, to create immunity in infants, and to allow protection to be conferred in advance through mass immunization programmes </li></ul>
  46. 49. Meningococcal vaccine <ul><ul><li>Meningococcal conjugate vaccine (MCV4) if preferred for adults aged 55 years or younger; meningococcal polysaccharide vaccine (MPSV4) is preferred for adults aged 56 years or older. </li></ul></ul><ul><ul><li>Revaccination with MCV4 after 5 years is recommended for adults previously vaccinated with MCV4 or MPSV4 who remain at increased risk for infection. </li></ul></ul>
  47. 50. Other Vaccines in Meningococcal Infection <ul><li>Other conjugate vaccines, including a heptavalent vaccine (DTP Hep B Hib) covering Sero groups A, and C, are being developed by the private sector; and a tetravalent vaccine has recently been licensed by Sanofi-Pasteur in the United States and Canada. </li></ul>
  48. 51. Zoster vaccine <ul><li>The zoster vaccine licensed in the United States (ZOSTAVAX®, Merck & Co., Inc.) is a lyophilized preparation of the Oka/Merck strain of live, attenuated VZV, the same strain used in the varicella vaccines (VARIVAX®, PROQUAD®). The Oka strain was isolated in Japan in the early 1970s from vesicular fluid from a healthy child who had varicella; the strain was attenuated through sequential propagation in cultures of human embryonic lung cells, embryonic guinea-pig cells, and human diploid cells (WI-38). </li></ul>
  49. 52. Zoster virus with Combination <ul><li>The more recently licensed live, attenuated Oka-strain VZV vaccine (PROQUAD®) prepared in combination with measles, mumps, and rubella vaccine (MMRV) is formulated with a broad range of titers that extend to over 60,000 PF </li></ul>
  50. 53. Duration of Efficacy and of Immunity <ul><li>Vaccine efficacy for zoster prevention declined during the first year following vaccination, but remained stable through the remaining 3 years of follow up Vaccine efficacy for PHN prevention had a similar pattern, with an initial decline and subsequent stabilization. </li></ul>
  51. 54. Site of Injection is important <ul><li>Zoster vaccine should be administered as a single 0.65-mL dose subcutaneously in the deltoid region of the upper arm; a booster dose is not licensed for the vaccine. The vaccine should not be injected intravascularly or intramuscularly and should only be reconstituted and injected using a sterile syringe free of preservatives, antiseptics, and detergents, which can inactivate the vaccine virus. </li></ul>
  52. 55. Vaccines for Hepatitis A <ul><li>Hepatitis A vaccines licensed in the United States are inactivated, whole-cell virus vaccines that are produced from hepatitis A virus grown in human diploid fibroblast cells. There are 2 single-antigen vaccines, Vaqta and Havrix, and a combined hepatitis A/hepatitis B vaccine, Twinrix (GlaxoSmithKline). The purified virus is then formalin inactivated and adsorbed to aluminum hydroxide. Havrix and Twinrix have 2-phenoxyethanol added as a preservative, whereas Vaqta is preservative free </li></ul>
  53. 56. U S adopts to New vaccine <ul><li>All children who live in the United States should receive hepatitis A vaccine at 1 year of age (ie, 12–23 months of age) as a 2-dose regimen. Immunization should be integrated into the routine childhood immunization schedule and completed according to the approved schedules using Havrix or Vaqta hepatitis A vaccines. Administration of 2 doses of the same hepatitis A </li></ul>
  54. 57. Japanese B encephalitis <ul><li>Japanese B encephalitis (JE), a mosquito-borne Arboviral infection, is the leading cause of viral encephalitis in Asia Approximately 50,000 sporadic and epidemic cases of JE are reported annually from the People's Republic of China (PRC), Korea, Japan, Southeast Asia, the Indian subcontinent, and parts of Oceania. </li></ul>
  55. 58. Prevalence of Japanese B Encepalitis
  56. 59. INACTIVATED JAPANESE B ENCEPHALITIS VIRUS VACCINE <ul><li>An inactivated JE vaccine derived from infected mouse brain has been licensed in Japan since 1954 (24). JE vaccine licensed in the United States is produced by the Research Institute of Osaka University (Biken) and is distributed by Connaught Laboratories Inc. The Biken vaccine is the most widely used JE vaccine of its type. </li></ul><ul><li>Similar mouse brain derived JE vaccines are produced by other manufacturers in India, Japan, Korea, Taiwan, Thailand, and Vietnam In the PRC, inactivated and attenuated JE vaccines are produced in primary hamster kidney cells </li></ul>
  58. 61. H1 N1 old infection and New Threat <ul><li>  H1N1 is a new virus that was first detected in people in April 2009. It was originally referred as “swine flu” because many of the genes in this new virus were similar to influenza viruses that occur in pigs . </li></ul>
  59. 62. Successful and Safe Vaccine for H1N1 <ul><li>The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, has conducted swine flu clinical trials to make sure the new swine flu vaccines are safe and effective. They were conducted at eight university research hospitals and medical organizations across the United States, including Baylor College of Medicine in Houston, Children's Hospital Medical Centre in Cincinnati, and Emory University in Atlanta. </li></ul>
  60. 63. Who should get Vaccinated for H1 N1 <ul><li>CDC recommends influenza vaccination as the first and most important step in protecting against the flu. CDC is encouraging anyone who wants to protect themselves against 2009 H1N1 to get vaccinated, including people 65 years and older. While less likely to get sick with 2009 H1N1 than younger people, people 65 and older are at high risk of serious complications if they do become ill. </li></ul>
  61. 64. FDA approved H1 N1 vaccines <ul><li>The U.S. Food and Drug Administration an has approved four vaccines against the 2009 H1N1 influenza virus </li></ul><ul><li>The vaccines are made by CSL Limited, MedImmune LLC, Novartis Vaccines and Diagnostics Limited, and sanofi pasteur Inc. All four firms manufacture the H1N1 vaccines using the same processes, which have a long record of producing safe seasonal influenza vaccine </li></ul>
  62. 65. Influenza A (H1N1) 2009 Monovalent Vaccine <ul><li>INDICATIONS AND USAGE </li></ul><ul><li>Influenza A (H1N1) 2009 Monovalent Vaccine is an inactivated influenza virus vaccine indicated for active immunization of persons 4 years of age and older against influenza disease caused by pandemic (H1N1) 2009 virus . </li></ul>
  63. 66. DOSAGE AND ADMINISTRATION <ul><li>Based on currently available information the vaccination regimen is as follows: </li></ul><ul><li>Children 4 through 9 years of age : Two 0.5-mL intramuscular injections approximately 1 month apart Children 10 through 17 years of age: A single 0.5-mL intramuscular injection </li></ul><ul><li>Adults 18 years of age and older: A single 0.5-mL intramuscular injection </li></ul>
  64. 67. Hepatitis B vaccination included in several Vaccination Programme <ul><li>Hepatitis B vaccines are effective and safe. Up to 95% of vaccinated individuals form effective antibodies when they get the vaccine and are protected from hepatitis B. In healthcare workers, high-risk public safety workers, dialysis patients, and sexual partners of infected persons, a blood test for antibodies is recommended after vaccination to ensure that the person produced antibodies. For the few who do not form antibodies, revaccination may improve response, especially in infants </li></ul>
  65. 68. Licensed Vaccines That Are Not Being Used Widely <ul><li>New/Improved: </li></ul><ul><li>• Hib: PRP-conjugates </li></ul><ul><li>• Pneumococcus: PS-conjugates </li></ul><ul><li>• Cholera: inactivated </li></ul><ul><li>• Rotavirus: live, attenuated </li></ul><ul><li>• Typhoid: Vi, Ty2la </li></ul><ul><li>• Pertussis: Acellular </li></ul><ul><li>• HAV: Inactivated </li></ul><ul><li>• Group A Meningococcus: PS-conjugates </li></ul><ul><li>• Rabies: Cell-culture based </li></ul><ul><li>• Varicella: Live-attenuated </li></ul>
  66. 69. Progress to prevent H Pylori <ul><li>H. pylori is among commonest bacterial infections in humans, and may be be transmitted by water and oral fecal spread. </li></ul><ul><li>Genomics may help understanding the pathogenesis of H. pylori infection and development of new therapies, including H. pylori –specific antimicrobial agents and vaccines </li></ul><ul><li>Enormous progress in studying the virulence factors of H. pylori and their variation, but not yet used in clinical practice </li></ul><ul><li>Px and Rx vaccination have been successful in animal models, but the translation to human vaccine remains difficult </li></ul><ul><li>These developments will be needed to prevent and treat this infection in areas of the world where there is a high prevalence of chronic infection </li></ul>
  67. 70. New Vaccine Strategies Vaccine development <ul><li>Purified (Subunits) Antigens vaccine e.g. Hepatitis B, Haemophilus influenza type b, RSV, Rotavirus, foot-and-mouth disease </li></ul><ul><li>Conjugate vaccines e.g. meningitis, pneumonia </li></ul><ul><li>Recombinant antigen vaccines e.g. Hepatitis B, malaria </li></ul>
  68. 71. Vaccine trails for HIV prevention
  69. 72. HIV Vaccine Approaches Protein subunit Synthetic peptide Naked DNA Inactivated Virus Live-attenuated Virus Live-vectored Vaccine
  70. 73. Challenges in HIV Vaccine Research <ul><ul><li>Viral Genetic Diversity : HIV is not just one specific virus. </li></ul></ul><ul><ul><li>Immune Protection : We don’t know what immune responses are needed, or how strong they need to be. </li></ul></ul><ul><ul><li>Neutralizing Antibody : Difficult to generate broadly neutralizing antibodies. </li></ul></ul><ul><ul><li>Vaccine Testing : Slow process, very expensive </li></ul></ul>
  71. 74. … but on the Brightside … <ul><li>Precedent from other systems : Success against other viral infections </li></ul><ul><li>Precedent from animal studies: Long-term control of infection in vaccinated monkeys </li></ul><ul><li>Immune control of HIV-1 : Infected individuals control infection </li></ul><ul><li>Vaccine Trials : In progress </li></ul>
  72. 75. Status of HIV Vaccine Development <ul><li>Over 60 Phase I/II trials of 30 candidate vaccines </li></ul><ul><ul><li>United States, Thailand, South Africa, Brazil </li></ul></ul><ul><li>One Phase III trial </li></ul><ul><ul><li>VaxGen gp120 protein subunit vaccine </li></ul></ul>
  73. 76. CDC collaborating the research on Vaccine for HIV infection <ul><li>CDC played an important role in the trials (VAX003 and VAX004) that evaluated the efficacy of gp120-based vaccine candidates. VaxGen, which also sponsored the trials. CDC sponsored a series of behavioural and biomedical studies linked to the VAX004 efficacy trial in North America and was part of the consortium that conducted the VAX003 trial in Thailand. Although the vaccine candidates failed to prevent HIV infection, the successful conduct of these trials proved that large HIV vaccine efficacy trials were possible, even in developing countries. </li></ul>
  74. 77. Difference between a preventive HIV vaccine and a therapeutic HIV vaccine? <ul><li>Therapeutic HIV vaccines are designed to control HIV infection in people who are already HIV positive Preventive HIV vaccines are designed to protect HIV negative people from becoming infected or getting sick. This fact sheet focuses on preventive HIV vaccines. </li></ul>
  75. 78. Malaria Vaccines in Progress
  76. 79. Vaccine trails in Malaria <ul><li>More than a dozen vaccine candidates are now in clinical development, and one, GlaxoSmithKline Biologicals’ RTS,S, is in Phase III clinical testing—the first malaria vaccine candidate to advance third stage of testing </li></ul>
  77. 80. Phase III trial in Malaria <ul><li>Phase III trial of the world’s most clinically advanced malaria vaccine candidate was launched in Kisumu, Kenya, in July 2009, under the auspices of the Kenya Medical Research Institute (KEMRI)/CDC Research and Public Health Collaboration. </li></ul>
  78. 81. Vaccine Candidate—GlaxoSmithKline Biological <ul><li>The vaccine candidate—GlaxoSmithKline Biological' (GSK Bio) RTS,S—is the first of the current generation of malaria vaccines to warrant Phase III testing on this scale. The vaccine has a promising safety profile, was more than 50% effective in reducing episodes of clinical malaria in children 5 to 17 months old in earlier testing, and can be administered together with the package of vaccinations routinely given to African children. </li></ul>
  79. 82. Very young taken for trails in view of High mortality and Morbidity <ul><li>Phase III trial will demonstrate how the vaccine performs in two groups of children—one aged 6 to 12 weeks and a second aged 5 to 17 months—in different transmission settings across a wide geographic region in Africa. </li></ul>
  80. 83. Malaria Vaccine possible in next few years <ul><li>In Phase II testing, the vaccine reduced cases of malaria in young children 5 to 17 months by 53%. If Phase III results are as good, the vaccine could be fully available in the next 5 - 10 years. </li></ul>
  81. 84. DNA Vaccines
  82. 85. DNA Vaccines <ul><li>DNA vaccines are at present experimental, but hold promise for future therapy since they will evoke both Humoral and Cell-mediated immunity, without the dangers associated with live virus vaccines. </li></ul>
  83. 86. What are DNA Vaccines ? From Scientific American , July 1995
  84. 87. Making DNA Vaccines <ul><li>The gene for an antigenic determinant of a pathogenic organism is inserted into a plasmid.  This genetically engineered plasmid comprises the DNA vaccine which is then injected into the host.  Within the host cells, the foreign gene can be expressed (transcribed and translated) from the plasmid DNA, and if sufficient amounts of the foreign protein are produced, they will elicit an immune response </li></ul>
  85. 88. Genetic Engineering a great tool in developing newer vaccines <ul><li>It is possible, using genetic engineering, to introduce a gene coding for an immunogenic protein from one organism into the genome of another (such as vaccinia virus). The organism expressing a foreign gene is called a recombinant. Following injection into the subject, the recombinant organism will replicate and express sufficient amounts of the foreign protein to induce a specific immune response to the protein. </li></ul>
  86. 89. Genetically Engineered Vaccines a future tool <ul><li>DNA vaccination is a technique for protecting an organism against disease by injecting it with genetically engineered DNA to produce an immunological response. Nucleic acid vaccines are still experimental, and have been applied to a number of viral, bacterial and parasitic models of disease, as well as to several tumour models. DNA vaccines have a number of advantages over conventional vaccines, including the ability to induce a wider range of immune response types. </li></ul>
  87. 90. DNA Vaccines are 3 rd Generation vaccines <ul><li>DNA vaccines are third generation vaccines , and are made up of a small, circular piece of bacterial DNA (called a plasmid) that has been genetically engineered to produce one or two specific proteins (antigens) from a micro-organism. The vaccine DNA is injected into the cells of the body, where the &quot;inner machinery&quot; of the host cells &quot;reads&quot; the DNA and converts it into pathogenic proteins. </li></ul>
  88. 91. Advantages of DNA Vaccines Over Other Types of Vaccines <ul><li>cheaper and easier to produce </li></ul><ul><li>safer </li></ul><ul><li>can elicit antibody and cellular immune responses </li></ul><ul><li>stable at a broad range of temperature (no cold-chain requirement) </li></ul><ul><li>can be designed and produced by genetic engineering to have only the desired antigens or antigenic sequences (epitopes) in the vaccine </li></ul>
  89. 92. The New GMO Swine Flu Corn Flakes <ul><li>Iowa State University researchers are putting flu vaccines into the genetic makeup of corn, which may someday allow pigs and humans to get a flu vaccination simply by eating corn or corn products. </li></ul>
  90. 93. WHO Initiative for Vaccine Research (IVR) <ul><li>The WHO Initiative for Vaccine Research was established in 2001 to streamline the various vaccine research and development projects being carried out by different departments of WHO (including the Special Programme for Research and Training in Tropical Diseases: TDR) and UNAIDS. </li></ul>
  91. 94. Importance Of Vaccines For Adults <ul><li>Most effective strategies for preventing illness </li></ul><ul><li>Deaths from VPD still occur </li></ul><ul><li>Viewed as routine for children and travelers but not for adults </li></ul><ul><li>Make immunizations integral part of patient care </li></ul>
  92. 95. Why we should support vaccination <ul><li>We don't vaccinate just to protect our children. We also vaccinate to protect our grandchildren and their grandchildren. With one disease, smallpox, we &quot;stopped the leak&quot; in the boat by eradicating the disease. Our children don't have to get smallpox shots any more because the disease no longer exists. If we keep vaccinating now, parents in the future may be able to trust that diseases like polio and meningitis won't infect, cripple, or kill children. </li></ul>
  93. 96. Vaccine Controversies <ul><li>The public health benefits of vaccinations are exaggerated. Critics of vaccination policy point out that the mortality rates of some illnesses were already dramatically reduced before vaccines were introduced, and claim that further reductions cannot immediately be attributed to vaccines. </li></ul><ul><li>Secondary and long-term effects on the immune system from introducing immunogens directly into the bloodstream are not fully understood. </li></ul>
  94. 97. Vaccine Controversies <ul><li>Vaccinations contain chemical components that are known to be toxic, such as formaldehyde, aluminum in various compounds, acetone, glyceride, ethylene glycol, and neomycin when injected in large enough quantities </li></ul>
  95. 98. Can some vaccines cause Cancers ? <ul><li>Some researchers hypothesize possible links between the increasing incidence of cancer and use of vaccines, suggesting links to the way vaccines may alter the cells in our bodies. </li></ul>
  96. 99. Vaccine development A Complex Research <ul><li>Vaccine development for emerging and re-emerging diseases is a complex issue </li></ul><ul><li>There are many mechanisms already in place to help deal with the development of preventive vaccines for emerging and re-emerging diseases </li></ul><ul><li>Close communication between the Sponsor and the Agency will hopefully aid in more efficient product development </li></ul>
  97. 100. Vaccines Can Contain Dangerous Ingredients Not Adequately Reported to the Public ?
  98. 101. Public do challenge the safety of Several Vaccines
  99. 102. Anti-vaccine lobbyists <ul><li>Not everybody believes that vaccines are good </li></ul><ul><li>Despite the ridiculousness of anti-vaccine arguments, there are significant and influential followers </li></ul><ul><li>They can bring untold damage to immunization programs and cause diseases and deaths </li></ul><ul><li>• Recent examples </li></ul><ul><li>– Northern Nigeria and polio </li></ul><ul><li>– MMR and measles in UK </li></ul><ul><li>– Hepatitis B in India </li></ul>
  100. 103. All the New Vaccines are Under Scanner by Health Authorities and Social Activists
  101. 104. Luc Montagnier on Vaccine for AIDS <ul><li>Our goal is not to completely eradicate the infection - that would be very difficult - but to produce a vaccine that will prevent not infection but disease. I think this is more possible. </li></ul><ul><li>It's clear that prevention will never be sufficient. That's why we need a vaccine that will be safe. </li></ul>
  102. 105. Are we getting the Vaccines in TIME
  103. 106. Created for Dr.T.V.Rao MD’s ‘e’ learning Programme Email [email_address]