Lack of induction of antibodies specific for conserved, discontinuous epitopes of HIV-1 envelope glycoprotein by candidate AIDS vaccines.
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.
VanCott
T C
TC
Division of Retrovirology, Walter Reed Army Institute of Research, Rockville, MD, USA.
Bethke
F R
FR
Burke
D S
DS
Redfield
R R
RR
Birx
D L
DL
D016915:AIDS Vaccines / Q000276:immunology*; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D000939:Epitopes / Q000276:immunology*; D015686:Gene Products, env / Q000097:blood / Q000276:immunology*; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000097:blood / Q000276:immunology; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41 / Q000097:blood / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000378:metabolism; D011489:Protein Denaturation; D011498:Protein Precursors / Q000097:blood / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
D016915:AIDS Vaccines; D000939:Epitopes; D015686:Gene Products, env; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D007106:Immune Sera; D011498:Protein Precursors; D014614:Vaccines, Synthetic