Combination effect on HIV infection in vitro of soluble CD4 and HIV-neutralizing antibodies

Hansen, Jan Erik; Sørensen, Anne Marie; Olofsson, Sigvard; Osinaga, Eduardo; Roseto, A.

doi:10.1007/bf01379116

Cited by 6 publications

(5 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2]), the potency of neutralization was reduced. This is the first time that antagonism has been shown between two anti-gp41 MAbs, although a similar antagonistic effect in HIV-1 neutralization has been previously reported with a pair of anti-gp120 MAbs directed against gp120 (with Abs to gp120 V3 and anti-gp120 CD4bd [40]). Antagonism between Abs has also been demonstrated in other virus systems (42,64).…”

Section: Discussionsupporting

confidence: 77%

“…Various combinations of human MAbs have been studied over the past several years which have shown additive, synergistic, or antagonistic effects on the neutralization of HIV-1 (13,14,40,55,57,58,61,62,81,91,92). In most of these studies, TCLA strains of HIV-1 were used, and most frequently the authors of these reports have used a computer model developed by Chou and Talalay (19) to analyze and define synergy.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Additive Effects Characterize the Interaction of Antibodies Involved in Neutralization of the Primary Dualtropic Human Immunodeficiency Virus Type 1 Isolate 89.6

Verrier¹,

Nádas

Gorny³

et al. 2001

J Virol

View full text Add to dashboard Cite

Human immunodeficiency virus-type I (HIV-1) infection elicits antibodies (Abs) directed against several regions of the gp120 and gp41 envelope glycoproteins. Many of these Abs are able to neutralize T-cell-lineadapted strains (TCLA) of HIV-1, but only a few effectively neutralize primary HIV-1 isolates. The nature of HIV-1 neutralization has been carefully studied using human monoclonal Abs (MAbs), and the ability of such MAbs to act in synergy to neutralize HIV-1 has also been extensively studied. However, most synergy studies have been conducted using TCLA strains. To determine the nature of Ab interaction in HIV-1 primary isolate neutralization, a panel of 12 anti-HIV-1 human immunoglobulin G (IgG) MAbs, specific for epitopes in gp120 and gp41, were used. Initial tests showed that six of these MAbs, as well as sCD4, used individually, were able to neutralize the dualtropic primary isolate HIV-1 89.6 ; MAbs giving significant neutralization at 2 to 10 g/ml included 2F5 (anti-gp41), 50-69 (anti-gp41), IgG1b12 (anti-gp120 CD4bd ), 447-52D (anti-gp120 V3 ), 2G12 (antigp120), and 670-D (anti-gp120 C5 ). For studies of reagent interaction, 16 binary combinations of reagents were tested for their ability to neutralize HIV-1 89.6 . Reagent combinations tested included one neutralizing MAb with sCD4, six pairs consisting of two neutralizing MAbs, and nine pairs consisting of one neutralizing MAb with another non-neutralizing MAb. To assess the interaction of the latter type of combination, a new mathematical treatment of reagent interaction was developed since previously used methods could be used only when both reagents neutralize. Synergy was noted between sCD4 and a neutralizing anti-gp120 V3 MAb. Antagonism was noted between two pairs of anti-gp41 MAbs (one neutralizing and one non-neutralizing). All of the other 13 pairs of MAbs tested displayed only additive effects. These studies suggest that Abs rarely act in synergy to neutralize primary isolate HIV-1 89.6

show abstract

Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Additive Effects Characterize the Interaction of Antibodies Involved in Neutralization of the Primary Dualtropic Human Immunodeficiency Virus Type 1 Isolate 89.6

Verrier¹,

Nádas

Gorny³

et al. 2001

J Virol

View full text Add to dashboard Cite

show abstract

“…The mAb 2G12 is a human IgG1/κ which recognizes a cluster of high‐mannose‐type N ‐glycans on the HIV envelope protein gp120 (Buchacher et al ., 1994; Trkola et al ., 1996). The 2G12 antibody has been demonstrated to have high neutralizing ability in vitro (Hansen et al ., 1994; Trkola et al ., 1995; Li et al ., 1997) and in animal models (Baba et al ., 2000; Mascola et al ., 2000). Although it has high efficacy on its own, for clinical application the antibody is currently being used in combination with other neutralizing HIV IgG1 antibodies, e.g.…”

Section: Introductionmentioning

confidence: 99%

Fluorescent protein fusions to a human immunodeficiency virus monoclonal antibody reveal its intracellular transport through the plant endomembrane system

Irons

Nuttall

Floß

et al. 2008

Plant Biotechnology Journal

View full text Add to dashboard Cite

SummaryIn order to further understand the production and intracellular trafficking of pharmaceutical proteins in plants, the light and heavy chains (LC and HC) of the human immunodeficiency virus neutralizing monoclonal antibody 2G12 were fused to fluorescent proteins [Venus and monomeric red fluorescent protein (mRFP)] to enable the visualization of their passage through the plant cell. Co-expression of LC and HC with various markers of the endomembrane system demonstrated that LC fusions were found in mobile punctate structures, which are likely to be pre-vacuolar compartments (PVCs) as a proportion of the LC fusions were found to be located in the vacuole. In addition, apoplast labelling was also observed with a 2G12LC-RFP fusion. The HC fusion expressed alone was found only in the endoplasmic reticulum (ER). When the LC and HC fusions were expressed together, they were found to co-locate to larger punctate structures, which were morphologically distinct from any observed on expression of LC or HC alone. These structures appeared to be in close association with the ER and their labelling partially overlapped with PVC marker fluorescence, but no increase in apoplast labelling was observed. Co-immunoprecipitation data demonstrated that the presence of the fluorescent proteins did not affect the assembly of the antibody, and also showed the association of BiP with the antibody chains.The antigen-binding activity of the Venus-fused 2G12 antibody was confirmed by enzyme-linked immunosorbent assay.

show abstract

“…Various combinations of human mAbs have been studied over the past several years which have shown additive, synergistic, or antagonistic effects on the neutralization of HIV-1 [130,131,132,133,134,135]. Antagonistic effect in HIV-1 neutralization has been previously reported with a pair of anti-gp120 mAbs directed against the V3-loop and the CD4 binding site, respectively [136]. The molecular mechanisms determining the antagonism have not been further studied in details.…”

Section: Human Immunodeficiency Virus (Hiv)mentioning

confidence: 99%

Neutralization Interfering Antibodies: A “Novel” Example of Humoral Immune Dysfunction Facilitating Viral Escape?

Mancini

Clementi

Diotti

et al. 2012

Viruses

View full text Add to dashboard Cite

The immune response against some viral pathogens, in particular those causing chronic infections, is often ineffective notwithstanding a robust humoral neutralizing response. Several evasion mechanisms capable of subverting the activity of neutralizing antibodies (nAbs) have been described. Among them, the elicitation of non-neutralizing and interfering Abs has been hypothesized. Recently, this evasion mechanism has acquired an increasing interest given its possible impact on novel nAb-based antiviral therapeutic and prophylactic approaches. In this review, we illustrate the mechanisms of Ab-mediated interference and the viral pathogens described in literature as able to adopt this “novel” evasion strategy.

show abstract

Combination effect on HIV infection in vitro of soluble CD4 and HIV-neutralizing antibodies

Abstract: In combination with HIV gp120 V3-loop antibody, two carbohydrate specific neutralizing antibodies (83D4 and 2G12) had a synergistic neutralizing effect on HIV infection. However, sCD4 and an antibody which blocks gp 120/CD4 binding (1B1) both displayed antagonism.

Cited by 6 publications

References 11 publications

Additive Effects Characterize the Interaction of Antibodies Involved in Neutralization of the Primary Dualtropic Human Immunodeficiency Virus Type 1 Isolate 89.6

Additive Effects Characterize the Interaction of Antibodies Involved in Neutralization of the Primary Dualtropic Human Immunodeficiency Virus Type 1 Isolate 89.6

Fluorescent protein fusions to a human immunodeficiency virus monoclonal antibody reveal its intracellular transport through the plant endomembrane system

Neutralization Interfering Antibodies: A “Novel” Example of Humoral Immune Dysfunction Facilitating Viral Escape?

Contact Info

Product

Resources

About