      Document 0080
 DOCN  DRG0080
 UNIQUE IDENTIFIER        DRG-0167
 NAME OF SUBSTANCE        rgp120/HIV-1MN Monovalent Octameric V3
                          Peptide Vaccine [NIAID VEU 011]
 SYNONYMS                 SynVac [NIAID VEU 011]
 PROTOCOL ID NUMBERS      NIAID VEU 011
 PROTOCOL ID NUMBERS      FDA 091
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: The V3 peptides are the
                          immunogenic portion of the multiple antigen
                          peptide, and the lysine core matrix is not
                          immunogenic. Immunogenicity studies with the
                          octameric IIIB V3 peptide formulated in alum
                          adjuvant have been carried out in a variety
                          of species including mice, rabbits and rhesus
                          macaques. Pre-clinical studies using guinea
                          pigs demonstrated that HIV-1 IIIB V3
                          octameric peptide induced high titer
                          anti-IIIB neutralizing antibody with
                          crossreactivity against RF and MN strains. A
                          300 microgram dose of MN V3 octameric peptide
                          formulated with alum given at 0, 4, and 8
                          weeks to African Green Monkeys induced ELISA
                          reciprocal antibody titers ranging as high as
                          10--5 and reciprocal virus neutralizing
                          antibody titers as high as 1,000 and ELISA
                          reciprocal antibody titers as high as 10,000.
                          Two of two pigtail macaques given a
                          multivalent V3 octameric peptide containing
                          20 micrograms of MN V3 octameric peptide
                          developed neutralizing antibodies. [NIAID VEU
                          011]
 DISEASES STUDIED/TREATED Prophylaxis against HIV infection [NIAID VEU
                          011]
 CLASSIFICATION CODE      Vaccine [NIAID VEU 011]
 ADVERSE EFFECTS          Adverse effects may include those associated
                          with intramuscular injection of any
                          polypeptide, such as pain, redness, and
                          swelling at the injection site, as well as
                          possible fever, chills, aches, pains, and
                          fatigue. [NIAID VEU 011]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Monovalent synthetic
                          vaccine based on eight V3-derived peptides
                          attached to a heptalysyl core to form
                          radial-octamers [NIAID VEU 011]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: The haptalysyl core bearing
                          eight reactive NH2-termini serves as a
                          carrier onto which eight V3 peptides are
                          attached by solid-phase synthesis [NIAID VEU
                          011]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: The antigenic principal
                          neutralizing determinant matrix, with an
                          8-fold molar excess of peptide over the core,
                          forms greater than 95 percent of the mass of
                          the octamer [NIAID VEU 011]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: 500 mcg vials. [NIAID VEU 011]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intramuscular. [NIAID VEU
                          011]
 SUBSTANCE DELIVERY DATA  STORAGE: Store between 2 and 8 C (35.6-46.4
                          F). [NIAID VEU 011]
 MANUFACTURERS            United Biomedical Inc
 REFERENCES               Fraisier C, Ebersold A, Blomberg J,
                          Desgranges C. Primary in vitro immunization
                          with multimeric synthetic peptides of HIV-1
                          envelope glycoproteins: generation of
                          neutralizing human monoclonal antibodies. J
                          Immunol Methods 1994 Nov 10;176(1):9-22.
 REFERENCES               Gorse GJ, Keefer M, Weinhold K, Matthews T,
                          Stablein D, Potts B, Forrest B. Phase I study
                          of HIV-1 MN V3 octameric peptide vaccine. Int
                          Conf AIDS. 1994 Aug 7-12;10(2):123 (abstract
                          no. PAO375).
 REFERENCES               Kahn J, Richardson J, Murcar N, Koff W,
                          Forrest B. Phase I study of HIV-1 MN
                          octameric V3 peptide vaccine in HIV-1
                          negative adults. Int Conf AIDS. 1994 Aug
                          7-12;10(1):91 (abstract no. 318a).
 REFERENCES               Morgado MC, Sabino EC, Shpaer EG, Bongertz V,
                          Brigido L, Guimaraes MD, Castilho EA,
                          Galvao-Castro B, Mullins JI, Hendry RM, et
                          al. V3 region polymorphisms in HIV-1 from
                          Brazil: prevalance of subtype B strains
                          divergent from North American/European
                          prototype and detection of subtype F. AIDS
                          Res Hum Retroviruses 1994 May;10(5):569-76.
 REFERENCES               Looney DJ, Li M, Walfield A, Hosein B, et al.
                          Type-specific and cross-reactive neutralizing
                          antisera against HIV elicited by V3-peptide
                          heptalysine octamers. AIDS Res Hum
                          Retroviruses. 1992 Aug;8(8):1381.
 REFERENCES               Walfield A, Li M, Hosien B, Ye J, Looney D,
                          Wong-Staal F, Morton W, Schmidt A, Wang CY.
                          High-titer neutralization for multiple HIV-1
                          isolates elicited by branched immunogens. Int
                          Conf AIDS. 1992 Jul 19-24;8(2):A41 (abstract
                          no PoA 2233).
 REFERENCES               Wang CY, Looney DJ, Li ML, Walfield AM, Ye J,
                          Hosein B, Tam JP, Wong-Staal F. Long-term
                          high-titer neutralizing activity induced by
                          octameric synthetic HIV-1 antigen. Science
                          1991 Oct 11;254(5029):285-8.
 ENTRY MONTH              9303
 LAST REVISION DATE       960403
 

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