      Document 0152
 DOCN  DRG0152
 UNIQUE IDENTIFIER        DRG-0095
 NAME OF SUBSTANCE        Recombinant p24 vaccine [Int Conf AIDS 1992
                          Jul 19-24;8(1):Tu39 (abstract no. TuB 0562)]
 SYNONYMS                 P24 (Recombinant) [AmFAR Tx Dir December
                          1990]
 SYNONYMS                 rp24 [AmFAR Tx Dir December 1990]
 SYNONYMS                 p24 Vaccine [Int Conf AIDS 1992 Jul
                          19-24;8(1): (abstract no. TuB 0562)]
 PROTOCOL ID NUMBERS      NIAID 90 I-170
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Infection with HIV has been
                          demonstrated to elicit antibody responses to
                          HIV-specific proteins, including the p24 core
                          and gp160 envelope proteins, although there
                          are variations in responses to the different
                          structural proteins from patient to patient.
                          While antibody titers to envelope protein
                          tend to remain high throughout all stages of
                          infection, antibody titers to the major core
                          antigen, p24, tend to be higher in
                          asymptomatic individuals and lower or falling
                          p24 antibody titers are associated with
                          clinical progression.  The in vivo HIV
                          antigen load is bimodal, characterized by a
                          rise after initial infection, a period of
                          latency of variable time, and an increase
                          again which correlates with progressive
                          stages of infection, as determined by various
                          methods of viral detection including
                          isolation of virus from peripheral blood
                          mononuclear cells and detection of free viral
                          core p24 protein.  A decline in p24 antibody
                          has been shown to precede the reappearance of
                          p24 antigenemia by as long as 18 months.
                          While it is possible that this observation
                          could be explained by viral events alone, it
                          is also possible that in vivo HIV expression
                          is initially regulated by an effective immune
                          response directed against HIV in natural
                          infection.  If the persistence or decline of
                          immune mechanisms such as p24 antibody level
                          determine whether or not HIV-infected
                          individuals have clinical progression of
                          disease, it may be possible to stimulate an
                          anamnestic response using an immunogen such
                          as p24 to enhance or prolong the asymptomatic
                          state and delay or prevent the development of
                          clinical disease. One clinical trial
                          experimented with using a combination of
                          recombinant gp160 and p24 vaccines. It was
                          concluded that recombinant gp160/p24 vaccines
                          (VaxSynR) administered to AIDS patients is
                          safe and well-tolerated. In patients with
                          initial CD4+ 200-500 cells/mm3,
                          immunogenicity was observed in 100% of
                          patients by month 6, and all patients have
                          remained clinically well for 12 months.
                          Improvements in mean and median CD4+ cell
                          counts were observed at months 4, 5, 6, and
                          in patients with initial CD4+ cells 200-500.
                          No statistically significant changes were
                          noted in individuals with initial CD4+ less
                          than 200, although individual improvements
                          have been noted. [Int Conf AIDS 1992 Jul
                          19-24;8(1):(abstract no. TuB 0562] [NIAID 90
                          I-170]
 DISEASES STUDIED/TREATED Primary HIV infection [Int Conf AIDS 1992 Jul
                          19-24;8(1): (abstract no. TuB 0562)]
 CLASSIFICATION CODE      Vaccine [Int Conf AIDS 1992 Jul
                          19-24;8(1):(abstract no. TuB 0562)]
 ADVERSE EFFECTS          Adverse effects may include inflammation at
                          the site of injection and effects associated
                          with immunizations in general. [AmFAR Tx Dir
                          December 1990] [NIAID 90 I-170]
 CONTRAINDICATIONS        Contraindicated in patients with known
                          hypersensitivity to insect cells or
                          baculovirus, leukopenia, anemia,
                          thrombocytopenia, significant hepatic or
                          renal dysfunction, malignancy (other than
                          Kaposi's sarcoma), clinically significant CNS
                          dysfunction as assessed by neurologic exam,
                          and those pregnant or nursing. [NIAID 90
                          I-170]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Noninfectious subunit
                          vaccine derived from synthetic Human
                          Immunodeficiency Virus Type I [HIV-1] core
                          protein [p24] produced in insect cells [NIAID
                          90 I-170] [AmFAR Tx Dir December, 1990]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: A baculovirus expression
                          vector containing the entire HIV-1 p24
                          protein, gag, is used to program cultured
                          insect cells to produce the synthetic HIV-1
                          core protein [NIAID 90 I-170] [AmFAR Tx Dir
                          December, 1990]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: The HIV-1 p24 is harvested
                          and purified from cultures of Lepidopteran
                          [insect] cells following exposure to
                          recombinant baculovirus vector [NIAID 90
                          I-170] [AmFAR Tx Dir December, 1990]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: The protein contained in
                          the vaccine is at least 95% pure and contains
                          no more than 5% insect cell and baculovirus
                          proteins [NIAID 90 I-170] [AmFAR Tx Dir
                          December, 1990]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: Recombinant p24 protein is
                          aluminum phosphate adsorbed [NIAID 90 I-170]
                          [AmFAR Tx Dir Dec 1990]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intramuscular (IM)
                          injection. [NIAID 90 I-170]
 MANUFACTURERS            MicroGeneSys
 REFERENCES               Blick G, Crook S, Buchanan S, Pelke I, Smith
                          G, Volvovitz F. A phase I/II trial evaluating
                          the combination use of recombinant GP160
                          (VaxSyn) and P24 vaccines vs. GP160 and
                          placebo by intradermal injection. Int Conf
                          AIDS. 1993 Jun 6-11;9(1):490 (abstract no.
                          PO-B27-2128).
 REFERENCES               Blick G, Crook S, Buchanan S, Smith G,
                          Volvovitz F. A phase I/II trial evaluating
                          the combination use of recombinant gp160
                          (VaxSyn) and P24 vaccines in HIV-seropositive
                          individuals regardless of initial CD4 cell
                          counts. Int Conf AIDS. 1993 Jun 6-11;9(1):490
                          (abstract no. PO-B27-2131).
 REFERENCES               Martin SJ, Weber J, Roitt I, Matear P, Jones
                          K, Vyakarnam A. Recombinant HIV-1 gag p24-Ty
                          virus-like particles (VLP's) induce HIV-1
                          p24-specific T helper cells in seronegative
                          volunteers vaccinated with these particles.
                          Int Conf AIDS. 1992 Jul 19-24;8(2):A35
                          (abstract no. PoA 2194).
 REFERENCES               Blick G, Buchanan S, Crook S, Diamond M,
                          Smith G, Volvovitz F. A phase I/II study of
                          the toxicity, immunogenicity and efficacy of
                          recombinant gp160 and p24 vaccines (VAXSYN)
                          in HIV infected individuals regardless of
                          CD4+ cell count. Int Conf AIDS. 1992 Jul
                          19-24;8(1):Tu39 (abstract no. TuB 0562).
 REFERENCES               Blick G, Buchanan S, Diamond M, Smith G,
                          Volvovitz F. Active immunization of
                          recombinant gp160/p24 vaccine (VAXSYN(R)) in
                          HIV-infected individuals: a community-based
                          phase I/II trial of toxicity and
                          immunogenicity. Int Conf AIDS. 1991 Jun
                          16-21;7(1):177 (abstract no. M.A.1343).
 ENTRY MONTH              9011
 LAST REVISION DATE       951109
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
