Neutralization of diverse human immunodeficiency virus type 1 variants by an anti-V3 human monoclonal antibody

Górny, Miroslaw K.; Conley, Anthony J.; Karwowska, Sylwia; Buchbinder, Aby; Xu, Jian-Yin; Emini, Emilio A.; Koenig, Scott; Zolla‐Pazner, Susan

doi:10.1128/jvi.66.12.7538-7542.1992

Cited by 300 publications

(167 citation statements)

References 41 publications

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“…MAbs used. MAb b12 was isolated by phage display (42), MAb 447-52D was isolated through hybridoma formation (41), and the remaining MAbs used here were isolated by VH and VL gene amplification from single B cells (11,43,44). The VH and VL gene usages of b12, PG9, 447-52D, and FI6 are provided in Table 1.…”

Section: Methodsmentioning

confidence: 99%

“…Interactions of 447-52D BCRs with recombinant Env. The V3 loop is a target of neutralizing antibodies against HIV-1, and MAb 447-52D is one of the most extensively characterized anti-V3 NAbs (41,(63)(64)(65)(66)(67). Although 447-52D is less potent and broad in its neutralizing activity than b12 or PG9 (25,68), it does neutralize diverse HIV-1 isolates.…”

Section: Expression and Functionality Of Exogenous Bcrs On The Surfacmentioning

confidence: 99%

“…PG9 recognizes a glycopeptide epitope located in the V1-V2 region and is derived from VH3-33 (11). MAb 447-52D recognizes elements of the V3 loop, derived from VH3-15, and displays narrower breadth of neutralizing activities than b12 or PG9 (25,41). Despite the fact that b12 and PG9 are derived from different VH genes, and despite the fact that their mutated forms recognize distinct Env regions on diverse Envs, the predicted germline forms of these antibodies did not display reactivity to any of the Envs tested here.…”

mentioning

confidence: 99%

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Diverse Recombinant HIV-1 Envs Fail To Activate B Cells Expressing the Germline B Cell Receptors of the Broadly Neutralizing Anti-HIV-1 Antibodies PG9 and 447-52D

McGuire

Glenn

Lippy

et al. 2014

J Virol

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Broadly neutralizing antibodies (bNAbsPotentially, this is the result of viral evolutionary mechanisms adopted to escape broadly neutralizing antibody responses. Our results also suggest that a single Env capable of activating germline BCRs that target distinct Env epitopes will be very difficult to identify or to design. IMPORTANCEBroadly neutralizing antibodies against HIV-1 are thought to be an important component of the immune responses that a successful vaccine should elicit. Broadly neutralizing antibodies are generated by a subset of those infected by HIV-1, but so far, they have not been generated by immunization with recombinant Envelope (Env, the target of anti-HIV-1 neutralizing antibodies). Here, we provide evidence that the inability of Env to elicit the production of broadly neutralizing antibodies is due to the inability of diverse Envs to engage the germline B cell receptor forms of known broadly neutralizing antibodies.

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Section: Methodsmentioning

confidence: 99%

Section: Expression and Functionality Of Exogenous Bcrs On The Surfacmentioning

confidence: 99%

mentioning

confidence: 99%

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Diverse Recombinant HIV-1 Envs Fail To Activate B Cells Expressing the Germline B Cell Receptors of the Broadly Neutralizing Anti-HIV-1 Antibodies PG9 and 447-52D

McGuire

Glenn

Lippy

et al. 2014

J Virol

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“…The mAbs used here were originally isolated in our lab from peripheral blood mononuclear cells (PBMCs) of HIV-1-infected individuals, using cellular (hybridoma) techniques described previously. The mAbs used in this study were re-expressed using recombinant technology as IgG 1 [21][22][23][24][25][26][27]. Monoclonal Abs 1357 [28], 1361 [28], 2158 [29], and 830A [26] are specific for the V2i epitope of gp120 as defined in Spurrier et al [30].…”

Section: Antibodiesmentioning

confidence: 99%

Primary Human Neutrophils Exhibit a Unique HIV-Directed Antibody-Dependent Phagocytosis Profile

et al. 2018

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The only clinical HIV vaccine trial to demonstrate efficacy, RV144, correlated protection with the antibodies (Abs) mediating function via the “constant” immunoglobulin region, the crystallizable fragment (Fc). These data have supported a focus on the induction of Abs by vaccines that trigger antiviral activities by relevant leukocytes via Fc receptors (FcRs). Neutrophils are phagocytes that comprise > 50% of leukocytes and display unique FcRs. We sought to compare the Ab-dependent cellular phagocytosis (ADCP) activity of human neutrophils to the commonly assayed THP-1 cell line. HIV-specific Abs were employed to elicit ADCP of beads coated with HIV envelope protein. Overall, trends were noted among neutrophil donors and the ADCP profile was different from that of THP-1 cells. mAb ELISA titers correlated with ADCP by THP-1 cells but not neutrophils. Monoclonal (m)Abs were also tested with primary monocytes. Donor-to-donor variation was high, and hindered the analysis of this dataset, but it was, in itself, an important finding. This study illustrates the concept that the assessment of FcR-mediated Ab activity with a frequently used cell line such as THP-1 is not necessarily indicative of relevant Ab functionality in vivo, and this calls for in-depth study of the properties of the HIV antibodies best-suited to eliciting antiviral activities by primary cells.

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“…Antisera that exhibit broadly neutralizing activity against diverse HIV-1 isolates have been observed in some long-term non-progressors (LTNP) (Braibant et al, 2006;Cecilia et al, 1999;Pilgrim et al, 1997). However, they are rare; despite over two decades of AIDS research, only a handful of broadly reactive Nabs (BR-Nabs) have been identified, including monoclonal antibodies (mAbs) b12, 2G12, 447-52D, 2F5, 4E10 and m48 (Gorny et al, 1992;Muster et al, 1993;Roben et al, 1994;Stiegler et al, 2001;Trkola et al, 1996;Zhang et al, 2006;Zwick et al, 2001). While the first three antibodies are gp120-specific, the latter three target gp41.…”

Section: Introductionmentioning

confidence: 99%

Assessment of antibody responses against gp41 in HIV-1-infected patients using soluble gp41 fusion proteins and peptides derived from M group consensus envelope

et al. 2008

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Human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein gp41 is targeted by broadly-reactive neutralizing antibodies 2F5 and 4E10, making it an attractive target for vaccine development. To better assess immunogenic properties of gp41, we generated five soluble glutathione S-transferase fusion proteins encompassing C-terminal 30, 64, 100, 142, or 172 (full-length) amino acids of gp41 ectodomain from M group consensus envelope sequence. Antibody responses in HIV-1-infected patients were evaluated using these proteins and overlapping peptides. We found (i) antibody responses against different regions of gp41 varied tremendously among individual patients, (ii) patients with stronger antibody responses against membrane-proximal external region exhibit broader and more potent neutralizing activity, and (iii) several patients mounted antibodies against epitopes that are near, or overlap with, those targeted by 2F5 or 4E10. These soluble gp41 fusion proteins could be an important source of antigens for future vaccine development efforts.

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Neutralization of diverse human immunodeficiency virus type 1 variants by an anti-V3 human monoclonal antibody

Abstract: The third variable region (V3) of the HIV-1 gpl20 envelope glycoprotein is thought to induce potent

Cited by 300 publications

References 41 publications

Diverse Recombinant HIV-1 Envs Fail To Activate B Cells Expressing the Germline B Cell Receptors of the Broadly Neutralizing Anti-HIV-1 Antibodies PG9 and 447-52D

Diverse Recombinant HIV-1 Envs Fail To Activate B Cells Expressing the Germline B Cell Receptors of the Broadly Neutralizing Anti-HIV-1 Antibodies PG9 and 447-52D

Primary Human Neutrophils Exhibit a Unique HIV-Directed Antibody-Dependent Phagocytosis Profile

Assessment of antibody responses against gp41 in HIV-1-infected patients using soluble gp41 fusion proteins and peptides derived from M group consensus envelope

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