Neutralizing antibodies from the sera of human immunodeficiency virus type 1-infected individuals bind to monomeric gp120 and oligomeric gp140.
Antibodies that neutralize primary isolates of human immunodeficiency virus type 1 (HIV-1) appear during HIV-1 infection but are difficult to elicit by immunization with current vaccine products comprised of monomeric forms of HIV-1 envelope glycoprotein gp120. The limited neutralizing antibody response generated by gp120 vaccine products could be due to the absence or inaccessibility of the relevant epitopes. To determine whether neutralizing antibodies from HIV-1-infected patients bind to epitopes accessible on monomeric gp120 and/or oligomeric gp140 (ogp140), purified total immunoglobulin from the sera of two HIV-1-infected patients as well as pooled HIV immune globulin were selectively depleted of antibodies which bound to immobilized gp120 or ogp140. After passage of each immunoglobulin preparation through the respective columns, antibody titers against gp120 and ogp140 were specifically reduced at least 128-fold. The gp120- and gp140-depleted antibody fraction from each serum displayed reduced neutralization activity against three primary and two T-cell line-adapted (TCLA) HIV-1 isolates. Significant residual neutralizing activity, however, persisted in the depleted sera, indicating additional neutralizing antibody specificities. gp120- and ogp140-specific antibodies eluted from each column neutralized both primary and TCLA viruses. These data demonstrate the presence and accessibility of epitopes on both monomeric gp120 and ogp140 that are specific for antibodies that are capable of neutralizing primary isolates of HIV-1. Thus, the difficulties associated with eliciting neutralizing antibodies by using current monomeric gp120 subunit vaccines may be related less to improper protein structure and more to ineffective immunogen formulation and/or presentation.
Stamatos
N M
NM
Division of Retrovirology, Walter Reed Army Institute of Research, Rockville, Maryland 20850, USA.
Mascola
J R
JR
Kalyanaraman
V S
VS
Louder
M K
MK
Frampton
L M
LM
Birx
D L
DL
VanCott
T C
TC
D016915:AIDS Vaccines / Q000276:immunology; D000595:Amino Acid Sequence; D001665:Binding Sites; D002460:Cell Line; D000939:Epitopes / Q000737:chemistry / Q000235:genetics; D015686:Gene Products, env / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011487:Protein Conformation; D013601:T-Lymphocytes; D054299:env Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D000939:Epitopes; D015686:Gene Products, env; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1