International Immunology, Vol 9, 1281-1290, Copyright © 1997 by Oxford University Press
CE Hioe, S Xu, P Chigurupati, S Burda, C Williams, MK Gorny and S Zolla-Pazner
To examine antibody-mediated neutralization of HIV-1 primary isolates in
vitro, we tested sera and plasma from infected individuals against four
clade B primary isolates. These isolates were analyzed further for
neutralization by a panel of several human anti-HIV-1 mAb in order to
identify the neutralizing epitopes of these viruses. Each of the HIV-1+
serum and plasma specimens tested had neutralizing activities against one
or more of the four primary isolates. Of the three individual sera, one
(FDA-2) neutralized all of the four isolates, while the other two sera were
effective against only one virus. The pooled plasma and serum samples
reacted broadly with these isolates. Based on the neutralizing activities
of the mAb panel, each virus isolate exhibited a distinct pattern of
reactivity, suggesting antigenic diversity among clade B viruses.
Neutralizing epitopes were found in the V3 loop and CD4- binding domain of
gp120, as well as near the transmembrane region (cluster II epitope) of
gp41. A mAb directed to the cluster I epitope of gp41 near the
immunodominant disulfide loop weakly neutralized one primary isolate. None
of the mAb in the panel affected one primary isolate, US4, although this
virus was sensitive to neutralization by some of the polyclonal antibody
specimens. This isolate was also resistant to neutralization by a cocktail
of 10 mAb, most of which individually inhibited at least one of the other
three viruses tested. These results suggest that neutralizing activity for
this latter virus is present in certain HIV-1+ sera/plasma, but is not
exhibited by the mAb in the panel. Thus, effective neutralizing antibodies
against primary isolates can be generated by humans upon exposure to HIV-1,
but not all of these antigenic specificities are represented in a large
panel of human anti-HIV-1 mAb.
ARTICLES
Neutralization of HIV-1 primary isolates by polyclonal and monoclonal human antibodies
New York University, Veterans Affairs Medical Centers, NY 10010, USA.
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