VACCINES

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VACCINES
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PROPHYLACTIC

• TO HIV NEGATIVE
• TO PREVENT INFECTION

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THERAPEUTIC

• TO HIV-POSITIVE
• TO BOOST IMMUNE SYSTEM TO FIGHT HIV

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KILLED VACCINE

• WHOLE VIRUS, KILLED - COAT, CORE,...
• DISRUPTED BY HEATING OR CHEMICAL TREATMENT TO
  KILL THE VIRUS
• E.G., SALK POLIO VACCINE

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LIVE VACCINE

• ATTENUATED WEAKENED
• VIRUS IS ABLE TO INFECT AND REPRODUCE AND
  STIMULATE IMMUNE SYSTEM, BUT UNABLE TO CAUSE
  DISEASE
• E.G., SABIN POLIO VACCINE

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VACCINE TRIALS - HIV/U.S.

• FEAR OF WHOLE VIRUS, KILLED OR ATTENUATED
• RATHER, USE PARTS OF HIV
• COAT PROTEIN GP120 OR GP160
• INTERNAL PROTEIN P24
• ALONE OR IN COMBINATION

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TRIAL STAGES

• PHASE I - SAFETY
• PHASE II - IMMUNE RESPONSE
• B CELLS gt ANTIBODY
• T8 CELLS gt T-KILLER ACTIVITY
• PHASE III - EFFICACY - PREVENT INFECTION?

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VACCINE TRIALS - U.S.COAT PROTEIN - GP120/160

• PHASE I - SAFE - YES
• PHASE II - IMMUNE RESPONSE - YES
• BOTH ARMS - B AND T
• PHASE III - EFFICACY?
• PREVENT INFECTION?

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PHASE III - EFFICACY - SURROGATE TEST

• INJECT LIVE, PATHOGENIC HIV TO VACCINEES?
  UNETHICAL
• SURROGATE TEST - DO ANTIBODIES OF VACCINEES BLOCK
  HIV INFECTION OF HUMAN CELLS?
• LAB STRAIN OF HIV - YES
• PRIMARY ISOLATES OF HIV - NO

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PHASE III - EFFICACY

• PREVENT INFECTION?

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DON FRANCIS, CDC TO GENENTECH TO VaxGen

• FDA - PHASE III APPROVAL
• REFORMULATED COAT
• U.S. 5,000 -STRAIN B - HIGH RISK GAY/HETEROS
• THAILAND 2,500 - STRAINS B E
• HIV-NEGATIVE, HIV ANTIBODY
• COMPLETION IN 2003

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THERAPEUTIC VACCINE TRIALS

• JONAS SALK IDEA - WHOLE, KILLED HIV TO
  HIV-POSITIVE
• BOOST IMMUNE RESPONSE, LOWER VIRAL LOAD OR
  ELIMINATE VIRUS

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THERAPEUTIC TRIALS

• REMUNE - IMMUNE RESPONSE CORPORATION, CARLSBAD
• FIRST 300 - EFFICACY NOT YET DEMONSTRATED
• FDA APPROVAL TO ENROLL MORE

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IMMUNE TRIALS - FUTURE

• DEVELOPING WORLD - 6 MILLION NEW INFECTIONS PER
  YEAR
• STRAIN SPECIFIC FOR EACH COUNTRY?
• COCKTAIL?

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VACCINE STUDIES?

• RATIONALIST- NEED EVIDENCE OF EFFICACY!
• EMPIRICIST - LEARN AS WE GO
• ETHICS OF DOING NOTHING?
• DON FRANCIS - THEORETICAL BABBLING OF CRITICS

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HIV - LIVE, ATTENUATED

• CHARLES FARTHING, AIDS HEALTHCARE FOUNDATION, LA
• IAPAC - INTERNATIONAL ASSOCIATION OF PHYSICIANS
  IN AIDS CARE - 5,500 MEMBERS
• RECRUIT A FEW HUNDREDS FOR TRIAL IN 2000

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LIVE, ATTENUATED

• MUTATE TO PATHOGENIC?
• SIV-D3 - SIV VACCINE
• ATTENUATED FOR ADULTS
• INFECTS AND KILLS NEONATES
• 10 YEARS, ADULTS TO S-AIDS
• ENTRY INTO DNA - RISK OF CANCER

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RETROVIRUS VACCINE?

• VACCINES DO NOT PREVENT INFECTION - THEY QUICKEN
  AND ENHANCE IMMUNE RESPONSE WHICH STOPS
  PROGRESSION OF INFECTION TO DISEASE
• RETROVIRUS INFECTION - VACCINE TOO LATE? HIV
  SEEDED THRU BODY

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PERVERSE OUTCOME

• VACCINE MAY BE LESS THAN 100 EFFECTIVE IN
  BLOCKING INFECTION
• VACCINEE FEELING PROTECTED, MIGHT CONTINUE RISK
  ACTIVITIES