MicroBio 160 1st Edition Lecture 27 Outline of Last Lecture I II Facts Diagnosis of HIV infection III Persons Living with Diagnosed or Undiagnosed HIV infection HIV Care Continuum Outcomes IV The Public s Experience with HIV Testing V VI VII VIII Facts Worldwide Different Countries Experiences Another Success Story AIDS Orphans Outline of Current Lecture I II Development of AIDS Vaccines The Superinfection Case III AIDS Vaccine Phase III Trial in Thailand IV The Reality of These Results V VI VII VIII IX X XI Andrew Stimpson How Some Vaccines Work How Preventative Vaccines Work Problems With Creating an AIDS vaccines Preventative Vaccine Strengths Therapeutic Vaccines What is the Alternative to a Vaccine These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute Current Lecture Development of AIDS Vaccines have been trying to find vaccine since HIV was discovered Preventive measures such as abstinence faithfulness and condom use have reduced the spread of HIV infection but have not stopped it There are no drugs that can cure HIV AIDS and drugs to treat the disease are expensive and not widely available in developing countries Experiment shows AIDS vaccine unlikely to give total protection from disease Merck Co therapeutic vaccine showed initial promise of keeping SIV levels low in infected monkeys Method was an attempt to induce killer T cell activation don t go after the pathogen they go after infected cells then destroy them o However 3 years into the study 75 of the monkeys to sickened and died 70 of individuals that are vaccinated must be immune News of Superinfection Case Harvard Medical School study where 14 newly infected patients were given ART for a few weeks then taken off to allow the immune system to detect the virus In effect trying to mimic a vaccine One man did extremely well after 2 rounds of on off medication HIV was practically undectedable However in the span of 1 month the HIV counts in his blood surged He was infected with a new strain that was 12 different from the original strain immune system wasn t recognizing it The patient had become superinfected with another strain and even though it was 88 identical to the first strain his immune system did not recognize the new strain Why is this important Vaccine researchers assumed that an effective vaccine would be made of samples of the 7 8 major classes of HIV currently circulating in the population The Harvard patient was infected with 2 HIV viruses that were different strains but the same class genetically very similar Even scarier his immune response to the treatment was stronger than that typically seen to vaccines AIDS Vaccine Phase III Trial in Thailand Vaccine ALVAC from Sanofi Pasteur and AIDSVAX originally developed by VaxGenInc Enrolled a total of 16 402 volunteers The results New infections occurred in 51 of the 8 197 given vaccine and in 74 of the 8 198 who received dummy shots that worked out to a 31 lower risk of infection for the vaccine group The reality of these results The vaccine did not protect those at high risk of HIV infection such as sex workers and intravenous drug users The protective effect was greatest in the first 12 months and then seemed to diminish When those who did not get all six vaccine shots were taken out of the analysis the positive result was statistically insignificant Andrew Stimpson Tested negative for HIV 14 months after 3 initial positive tests While there have been anecdotal reports from Africa of people fighting off the virus this case is the first medically documented one He contracted the disease from his HIV positive boyfriend He had flu like symptoms and had 3 HIV antibody tests at the Victoria Clinic for Sexual Health in west London In October 2003 he was offered another test which came back negative This was followed by 2 more negative results confirming his HIV negative status He spent weeks meeting with leading HIV specialists immunologists and virologists After many tests there was still no answer as to what had actually happened The conclusion is that somehow during those 14 months he had gone from HIV positive to HIV negative Explanations He had 3 consecutive false positive tests The temporary presence of malformed HIV particles which were unable to successfully establish an ongoing infection Developing a sort of immunization through repeated exposure to HIV or its component proteins which would produce a natural antibody response against HIV Spontaneous seroreversion when the body stops producing antibodies against a protein despite the ongoing presence of the virus this is a type of immune tolerance o An important note the more specific and sensitive RT PCR test for HIV s genome does not appear to have been performed More Examples Prostitutes in India with frequent recurrent exposure to HIV seem to be immune Exposed seronegatives with negative RT PCR results This immunity disappears if they leave the profession and then return after several years 2 infants have been seemingly cured of HIV in the United States All of these suggest that a vaccine is possible if we can figure out how these individuals are protected by their immune systems How Some Vaccines Work Modified Live Vaccines contain an attenuated or weakened version of a disease agent These vaccines create a mild form of the disease that stimulates a natural immune response Modified live vaccines are effective but can negatively impact the health of the animal MMR OPV Chicken pox Killed Vaccines contain an inactivated disease causing agent These vaccines are designed to create antibodies without the negative effects of infection so are generally considered to be safe However during the inactivation process some of the surface antigens needed to create the desired antibodies may be destroyed thus reducing their effectiveness Inactivated Influenza IPV Subunit Vaccines use only the necessary parts of the virus to stimulate immunity Unlike modified live vaccines subunit vaccines stimulate the immune system to prevent disease without stressing the animal And unlike killed vaccines subunit vaccines do a better job of disease prevention as they only contain concentrated amounts of the target antigen These qualities make subunit vaccines both safe and effective Hib HepB HepA Pneumococcal conj Vaccine How Protective Vaccines Work During vaccination a vaccine with dead or harmless forms of viruses bacteria or
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