MicroBio 160 1st Edition Lecture 27Outline of Last Lecture I. FactsII. Diagnosis of HIV infectionIII. Persons Living with Diagnosed or Undiagnosed HIV infection HIV Care Continuum OutcomesIV. The Public’s Experience with HIV TestingV. Facts Worldwide VI. Different Countries ExperiencesVII. Another Success StoryVIII. AIDS OrphansOutline of Current Lecture I. Development of AIDS VaccinesII. The Superinfection CaseIII. AIDS Vaccine Phase III Trial in ThailandIV. The Reality of These ResultsV. Andrew StimpsonVI. How Some Vaccines WorkVII. How Preventative Vaccines WorkVIII. Problems With Creating an AIDS vaccinesIX. Preventative Vaccine StrengthsX. Therapeutic VaccinesXI. What is the Alternative to a VaccineThese 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 LectureDevelopment 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, theygo 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, tryingto 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 (immunesystem 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 strainWhy 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 vaccinesAIDS 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 groupThe 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 insignificantAndrew 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 andhad 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 negativeExplanations? :- 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 toleranceo An important note… the more specific and sensitive RT-PCR test for HIV's genome does not appear to have been performedMore 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 systemsHow 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. Unlikemodified 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
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