scholarly journals Oligomer-Specific Conformations of the Human Immunodeficiency Virus (HIV-1) gp41 Envelope Glycoprotein Ectodomain Recognized by Human Monoclonal Antibodies

2009 ◽  
Vol 25 (3) ◽  
pp. 319-328 ◽  
Author(s):  
Wen Yuan ◽  
Xing Li ◽  
Marta Kasterka ◽  
Miroslaw K. Gorny ◽  
Susan Zolla-Pazner ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Monoclonal Antibodies ◽  
Envelope Glycoprotein ◽  
Human Monoclonal Antibodies ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Gp41 Envelope

scholarly journals Human Immunodeficiency Virus Type 1 Monoclonal Antibodies Suppress Acute Simian-Human Immunodeficiency Virus Viremia and Limit Seeding of Cell-Associated Viral Reservoirs

2015 ◽  
Vol 90 (3) ◽  
pp. 1321-1332 ◽  
Author(s):  
Diane L. Bolton ◽  
Amarendra Pegu ◽  
Keyun Wang ◽  
Kathleen McGinnis ◽  
Martha Nason ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Antiretroviral Therapy ◽  
Envelope Glycoprotein ◽  
Plasma Viremia ◽  
Immunodeficiency Virus ◽  
Acute Hiv ◽  
Hiv 1

ABSTRACTCombination antiretroviral therapy (cART) administered shortly after human immunodeficiency virus type 1 (HIV-1) infection can suppress viremia and limit seeding of the viral reservoir, but lifelong treatment is required for the majority of patients. Highly potent broadly neutralizing HIV-1 monoclonal antibodies (MAbs) can reduce plasma viremia when administered during chronic HIV-1 infection, but the therapeutic potential of these antibodies during acute infection is unknown. We tested the ability of HIV-1 envelope glycoprotein-specific broadly neutralizing MAbs to suppress acute simian-human immunodeficiency virus (SHIV) replication in rhesus macaques. Four groups of macaques were infected with SHIV-SF162P3 and received (i) the CD4-binding-site MAb VRC01; (ii) a combination of a more potent clonal relative of VRC01 (VRC07-523) and a V3 glycan-dependent MAb (PGT121); (iii) daily cART, all on day 10, just prior to expected peak plasma viremia; or (iv) no treatment. Daily cART was initiated 11 days after MAb administration and was continued for 13 weeks in all treated animals. Over a period of 11 days after a single administration, MAb treatment significantly reduced peak viremia, accelerated the decay slope, and reduced total viral replication compared to untreated controls. Proviral DNA in lymph node CD4 T cells was also diminished after treatment with the dual MAb. These data demonstrate the virological effect of potent MAbs and support future clinical trials that investigate HIV-1-neutralizing MAbs as adjunctive therapy with cART during acute HIV-1 infection.IMPORTANCETreatment of chronic HIV-1 infection with potent broadly neutralizing HIV-1 MAbs has been shown to significantly reduce plasma viremia. However, the antiviral effect of MAb treatment during acute HIV-1 infection is unknown. Here, we demonstrate that MAbs targeting the HIV-1 envelope glycoprotein both suppress acute SHIV plasma viremia and limit CD4 T cell-associated viral DNA. These findings provide support for clinical trials of MAbs as adjunctive therapy with antiretroviral therapy during acute HIV-1 infection.

scholarly journals Determinants of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Activation by Soluble CD4 and Monoclonal Antibodies

1998 ◽  
Vol 72 (8) ◽  
pp. 6332-6338 ◽  
Author(s):  
Nancy Sullivan ◽  
Ying Sun ◽  
James Binley ◽  
Juliette Lee ◽  
Carlos F. Barbas ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Monoclonal Antibodies ◽  
Envelope Glycoprotein ◽  
Envelope Glycoproteins ◽  
V3 Loop ◽  
Immunodeficiency Virus ◽  
Cd4 Binding Site ◽  
Hiv 1 ◽  
Soluble Cd4

ABSTRACT Infection by some human immunodeficiency virus type 1 (HIV-1) isolates is enhanced by the binding of subneutralizing concentrations of soluble receptor, soluble CD4 (sCD4), or monoclonal antibodies directed against the viral envelope glycoproteins. In this work, we studied the abilities of different antibodies to mediate activation of the envelope glycoproteins of a primary HIV-1 isolate, YU2, and identified the regions of gp120 envelope glycoprotein contributing to activation. Binding of antibodies to a variety of epitopes on gp120, including the CD4 binding site, the third variable (V3) loop, and CD4-induced epitopes, enhanced the entry of viruses containing YU2 envelope glycoproteins. Fab fragments of antibodies directed against either the CD4 binding site or V3 loop also activated YU2 virus infection. The activation phenotype was conferred on the envelope glycoproteins of a laboratory-adapted HIV-1 isolate (HXBc2) by replacing the gp120 V3 loop or V1/V2 and V3 loops with those of the YU2 virus. Infection by the YU2 virus in the presence of activating antibodies remained inhibitable by macrophage inhibitory protein 1β, indicating dependence on the CCR5 coreceptor on the target cells. Thus, antibody enhancement of YU2 entry involves neither Fc receptor binding nor envelope glycoprotein cross-linking, is determined by the same variable loops that dictate enhancement by sCD4, and probably proceeds by a process fundamentally similar to the receptor-activated virus entry pathway.

scholarly journals Antibody Neutralization-Resistant Primary Isolates of Human Immunodeficiency Virus Type 1

1998 ◽  
Vol 72 (12) ◽  
pp. 10270-10274 ◽  
Author(s):  
Paul W. H. I. Parren ◽  
Meng Wang ◽  
Alexandra Trkola ◽  
James M. Binley ◽  
Martin Purtscher ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Monoclonal Antibodies ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Escape Mutant ◽  
Human Monoclonal Antibodies ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Although typical primary isolates of human immunodeficiency virus type 1 (HIV-1) are relatively neutralization resistant, three human monoclonal antibodies and a small number of HIV-1+ human sera that neutralize the majority of isolates have been described. The monoclonal antibodies (2G12, 2F5, and b12) represent specificities that a putative vaccine should aim to elicit, since in vitro neutralization has been correlated with protection against primary viruses in animal models. Furthermore, a neutralization escape mutant to one of the antibodies (b12) selected in vitro remains sensitive to neutralization by the other two (2G12 and 2F5) (H. Mo, L. Stamatatos, J. E. Ip, C. F. Barbas, P. W. H. I. Parren, D. R. Burton, J. P. Moore, and D. D. Ho, J. Virol. 71:6869–6874, 1997), supporting the notion that eliciting a combination of such specificities would be particularly advantageous. Here, however, we describe a small subset of viruses, mostly pediatric, which show a high level of neutralization resistance to all three human monoclonal antibodies and to two broadly neutralizing sera. Such viruses threaten antibody-based antiviral strategies, and the basis for their resistance should be explored.

scholarly journals Synergistic Neutralization of Simian-Human Immunodeficiency Virus SHIV-vpu+ by Triple and Quadruple Combinations of Human Monoclonal Antibodies and High-Titer Anti-Human Immunodeficiency Virus Type 1 Immunoglobulins

1998 ◽  
Vol 72 (4) ◽  
pp. 3235-3240 ◽  
Author(s):  
An Li ◽  
Hermann Katinger ◽  
Marshall R. Posner ◽  
Lisa Cavacini ◽  
Susan Zolla-Pazner ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Monoclonal Antibodies ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
High Titer ◽  
Triple Combination ◽  
Human Monoclonal Antibodies ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT We have tested triple and quadruple combinations of human monoclonal antibodies (MAbs), which are directed against various epitopes on human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins, and a high-titer anti-HIV-1 human immunoglobulin (HIVIG) preparation for their abilities to neutralize a chimeric simian-human immunodeficiency virus (SHIV-vpu+). This virus encodes the HIV-1 strain IIIB env, tat, rev, and vpu genes. The quantitative nature of the Chou-Talalay method (Adv. Enzyme Regul. 22:27–55, 1984) allows ranking of various combinations under identical experimental conditions. Of all triple combinations tested, the most potent neutralization was seen with MAbs 694/98D plus 2F5 plus 2G12 (directed against domains on V3, gp41, and gp120, respectively) as measured by the total MAb concentration required to reach 90% neutralization (90% effective concentration [EC90], 2.0 μg/ml). All triple combinations involving MAbs and/or HIVIG that were tested yielded synergy with combination index values of <1; the dose reduction indices (DRIs) ranged from 3.1 to 26.2 at 90% neutralization. When four MAbs (the previous three plus MAb F105, directed against the CD4 binding site) were combined, higher neutralization potency (EC90, 1.8 μg/ml) and a higher degree of synergy compared to any triple combination were seen. The mean DRIs of the quadruple combination were approximately twice that of the most synergistic triple combination. We conclude that human MAbs targeting different HIV-1 envelope glycoprotein epitopes exhibit strong synergy when used in combination, a fact that could be exploited clinically for passive immunoprophylaxis against HIV-1.

scholarly journals The convertases furin and PC1 can both cleave the human immunodeficiency virus (HIV)-1 envelope glycoprotein gp160 into gp120 (HIV-1 SU) and gp41 (HIV-I TM).

1994 ◽  
Vol 269 (16) ◽  
pp. 12240-12247 ◽  
Author(s):  
E. Decroly ◽  
M. Vandenbranden ◽  
J.M. Ruysschaert ◽  
J. Cogniaux ◽  
G.S. Jacob ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Envelope Glycoprotein ◽  
Immunodeficiency Virus ◽  
Hiv 1
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