       Document 0399
 DOCN  M9610399
 TI    Lack of induction of antibodies specific for conserved, discontinuous
       epitopes of HIV-1 envelope glycoprotein by candidate AIDS vaccines.
 DT    9601
 AU    VanCott TC; Bethke FR; Burke DS; Redfield RR; Birx DL; Division of
       Retrovirology, Walter Reed Army Institute of; Research, Rockville, MD,
       USA.
 SO    J Immunol. 1995 Oct 15;155(8):4100-10. Unique Identifier : AIDSLINE
       MED/96003456
 AB    We examined the humoral immune response in both HIV-1 infected and
       uninfected volunteers immunized with candidate HIV-1 recombinant
       envelope subunit vaccines (Genentech gp120IIIB, MicroGeneSys gp160IIIB,
       or ImmunoAG gp160IIIB). Immunization of both HIV-1 infected and
       uninfected volunteers with these immunogens resulted in the induction of
       Abs preferentially reactive with epitopes accessible on a denatured form
       of gp120. While sera from HIV-1 uninfected gp120/gp160IIIB vaccinees
       bound gp120/gp41, which was expressed on the surface of H9 cells
       infected with HIV-1IIIB, minimal binding to HIV-1MN or HIV-1RF infected
       cells was obtained. Induction of qualitatively similar immune responses
       by these immunogens would not have been predicted based on their
       different tertiary structures. These data indicate a restriction of the
       immune response to linear, conserved epitopes poorly accessible on both
       monomeric gp120 and cell-surface expressed oligomeric gp120/gp41 and a
       lack of Abs specific for conformational epitopes conserved across
       divergent HIV-1 strains. Poor recognition of HIV-1 envelope tertiary and
       quaternary structure may explain the restricted neutralization profiles
       of vaccinee sera against laboratory-adapted strains of HIV-1 and their
       inability to neutralize primary HIV-1 isolates. Alternate immunogens or
       reformulations with the capacity to elicit Abs that preferentially bind
       to natively folded gp120 should be investigated and correlated with
       their ability to neutralize more diverse laboratory-adapted and primary
       HIV-1 isolates.
 DE    AIDS Vaccines/*IMMUNOLOGY  Binding Sites, Antibody  Binding, Competitive
       Epitopes/*IMMUNOLOGY  Gene Products, env/BLOOD/*IMMUNOLOGY  Human  HIV
       Antibodies/*BIOSYNTHESIS/BLOOD  HIV Envelope Protein
       gp120/BLOOD/IMMUNOLOGY  HIV Envelope Protein gp41/BLOOD/IMMUNOLOGY
       Immune Sera/METABOLISM  Protein Denaturation  Protein
       Precursors/BLOOD/IMMUNOLOGY  Vaccines, Synthetic/IMMUNOLOGY  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

