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Journal of Virology, December 1998, p. 9656-9667, Vol. 72, No. 12
Division of Retrovirology,
Received 1 July 1998/Accepted 9 September 1998
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.
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Neutralizing Antibodies from the Sera of Human Immunodeficiency
Virus Type 1-Infected Individuals Bind to Monomeric gp120 and
Oligomeric gp140

*
Corresponding author. Mailing address: Henry M. Jackson
Foundation, 13 Taft Ct., Suite 200, Rockville, MD 20850. Phone: (301) 762-0089. Fax: (301) 762-4177. E-mail:
tvancott{at}hiv.hjf.org.
Present address: Institute of Human Virology and Department of
Medicine, University of Maryland, Baltimore, MD 21201-1192.
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