Term
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Definition
-body is challenged with infectious organism
-immune system (3rd line) responds with:
memory cells
antibodies
T-lymphocytes |
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Term
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Definition
-expose person to an infectious organism that is antigenic but not pathogenic
-must: not cause disease, have long-lasting effects, and be easy to administer |
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Term
| Vaccine Type 1. Killed whole cell or inactivated virus |
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Definition
-cultivate organism
-kill organism with heat, radiation, or formalin to destroy pathogenicity so that it cannot multiply in the body
-inoculate the patient with entire organism that is dead
-requires high doses and boosters (multiple injections)
-side effects (possible allergic reactions) |
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Term
| Vaccine Type 2: Live attenuated cells or virus |
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Definition
-organism can grow in body (produces more antigens = greater immune response)
-lessen the virulence
-requires lower doses and fewer boosters
-living organisms require special storage
-organism can be transmitted
-possible to mutate back to virulent form (danger!) |
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Term
| Vaccine Type 3: Subcellular or Subunit |
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Definition
-obtain an antigenic determinant from surface of organism and inject into patient
-AD purified form cultures or synthesized chemically
-safe - not injecting the whole actual organism
-not as antigenic (wont be as many antigens)
-requires large doses and boosters |
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Term
| Vaccine Type 4: Genetically Engineered (Recombinant) |
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Definition
-"trojan horse" style
1. extract DNA sequence that codes for protein antigens from organism's genome
2. insert DNA into plasmid
3. plasmid inject directly into patient or integrated into bacterium/virus vector then into patient
4. host (patient) cells accept plasmid and DNA is transcribed and translated
5. protein of pathogen is expressed on cell membrane, evoking an immune respone |
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Term
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Definition
1. genes that encode for antigenic determinants on HIV surface mutate frequently so immunity may not be effective after mutations
2. HIV is a provirus - not affected by antibodies
-cannot eliminate HIV from cells
3. HIV destroys T-lymphocytes
4. HIV is deadly so testing could be unethical and there are safety issues
5. HIV is a retrovirus - they do not elicit sufficient amounts of antibodies to prevent infection
6. Attenuated HIV vaccine can mutate and become pathogenic
7. Genes of inactivated whole virus can integrate into human chromosome
-retroviruses are known to cause cancer
8. there are multiple HIV strains with different ADs on surface
9. limited animal models for testing (it's a human virus)
-can use a HIV/SIV hybrid with chimps, but they're endangered (only 1500 available in US for ALL research), can't afford to kill them in testing |
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Term
| Strategies: 1. Sterilizing immunity |
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Definition
-protects an uninfected individual from future infection
-prevents HIV from multiplying and infecting as a provirus
-eliminated by the body |
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Term
| Strategies 2. Therapeutic immunity |
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Definition
-treating an already infected individual
-boost their immune system with vaccine so they can fight HIV
-prolong life of HIV patient
-prevent progression to AIDS
-reduce viral load
-delay debilitating symptoms (ARC)
-reduce economic pressure of health care system |
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Term
| Strategies 3. Perinatal immunity |
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Definition
-administer to pregnant women who are HIV+
-prevent transmission to fetus |
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Term
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Definition
targets: gp120 (mutates less frequently), gp41, gp160, p17, tat protein (we know genome sequences for these)
1.use reverse transcriptase and viral RNA as template to make HIV DNA for a specific gene
2. gene ligated into plasmid
3. plasmid inserted into E.coli
4. recombinant E.coli grown in large cultures
5. transcribes and translates HIV gene and secretes protein
6. purify massive amounts of specific protein
7. use as vaccine
8. immune system responds and generates anti-protein antibodies
problem: proteins are not engulfed by macrophages so there is a limited amount of antibodies |
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Term
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Definition
-trojan horse style
1. use vaccinia, adenovirus, canaryvirus, or bacterium (salmonella) and genetically engineer it to incorporate HIV genes (gag, env, pol) into genome
2. grow large amount of recombinant vector
3. inoculate patient with recombinant vector
4. HIV gene is expressed on the surface of vector
5. immune system responds and makes antibodies, memory cells, and T-cells
benefit: make more antibodies and memory/T-cells (since macrophages swallow them). also, it grow in host = stronger immune response and it responds to entire organism not just the ADs |
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Term
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Definition
-involves multiple HIV proteins = strong response
1. people with HIV-2 are protected against HIV-1
2. HIV+ people who lack nef gene don't progress to AIDS
-Desrosiers at Harvard injected monkeys with 2 forms of SIV (one form lacked 3 SIV genes while the other lacked the nef gene)
-then he challenged monkeys with the complete SIV strains - they resisted infection
= vaccination with inactive SIV protects against infection with active SIV
= little (low amounts) free SIV in the tissues
=T-cell counts were normal
problems: achieving complete inactivation, all it takes is 1
-possible mutation back to virulence
-cancer causing |
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Term
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Definition
-plasmids SIV gag and HIV env
-vaccinated monkeys with it, then challenged with active HSIV hybrid (SIV DNA with HIV proteins)
= monkeys were healthy: low ABs but high T-cells and undetectable HSIV levels |
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Term
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Definition
1. inject engineered, live virus with HIV env proteins (causes T-cell production)
2. boost with recombinant surface protein subunits (causes antibody production) |
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Term
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Definition
-in 2011 there were 30 clinical trials using 40 different vaccine in4 continents in 24 countries
-in 2005 the most advance trial took place
-adenovirus vector vaccine
-tried and failed and abandoned trial in 2007
-in 2010 the NIAID Vaccine Research Center discovered antibodies that prevent multiple HIV strains from infecting CD4 cells
-VRCO1 and VRCO2: found in blood of 60 year old non-progressor. produced by memory specific B-cells (very rare) and isolated 28 cells out of 25 million screened
-VRCO1 and VRCO2 bind to gp120
we spend: $40 billion/yr on HIV /AIDS research
$1 billion/yr on vaccine development for HIV
2005-2010: US spent $800 million/yr on vaccine research (only 1% of total AIDS budget)
costs: $50-100 million to identify vaccine
$100-200 million for production plant construction |
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