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Neutralization and infectivity characteristics of envelope glycoproteins from human immunodeficiency virus type 1 (HIV-1) infected donors whose sera exhibit broadly cross-reactive neutralizing (BCN) activity

Tuesday, 25 April, 2006 - 17:00
Campus: Brussels Health Campus
Faculty: Medicine and Pharmacy
auditorium P. Brouwer
Fatim Cham
phd defence

The complex architecture of the HIV-1 envelope
glycoprotein (Env), the major target of neutralizing
antibodies, enables its escape from antibodies
elicited during natural HIV-1 infection. Nonetheless,
broadly cross-reactive monoclonal antibodies and
polyclonal sera that can neutralize diverse primary
isolates have been identified in some chronically
infected patients. One such serum was identified
from a long-term non-progressor whose Env (R2)
elicited broadly cross-reactive antibodies that
correlated with protection against pathogenic SHIV
challenge. Therefore, we studied neutralization
properties of Envs encoded by viruses infecting
donors whose serum exhibits broad crossneutralizing
(BCN) activity. Characterization of BCN
and non-BCN Envs revealed that BCN Envs exhibited
properties that may be associated with induction of
BCN antibodies against the non-immunogenic
membrane proximal external region (MPER) of
gp41. This is the first study to identify 2F5 escape
variants in vivo, as a result of neutralizing HIV-1
serum. Immunogenicity studies are in progress in
animal models. Additionally, neutralization
properties of the circulating recombinant form
CRF07_B'C, were studied. Our data suggest that
emergence of recombinant primary isolates may
further contribute to primary virus escape from
neutralization. We have developed a panel of
infectious Env clones representative of the HIV-1
diversity. The panel confirmed breadth and potency
of two novel Mabs M14 and M18, recognizing
conformational epitopes overlapping receptor
and/or co-receptor binding sites.