Identification and specificity of broadly neutralizing antibodies against <scp>HIV</scp>

McCoy, Laura E.; Burton, Dennis R.

doi:10.1111/imr.12484

Cited by 210 publications

(198 citation statements)

References 105 publications

(249 reference statements)

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“…The first generation of bNAbs to HIV-1 (monoclonal antibodies such as b12, 2G12, 2F5, and 4E10) were isolated by phage display or B cell immortalization, and selected for binding to Env peptides or proteins [42]. This was followed by B cell culture and micro-neutralization (functional) screens, and by the use of flow cytometry-based isolation of single B cells using peptide and protein “baits”.…”

Section: Broadly Neutralizing Antibodiesmentioning

confidence: 99%

The Neutralizing Antibody Response to the HIV-1 Env Protein

Moore

2018

CHR

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Objective: Background:A vaccine able to elicit broadly neutralizing antibodies capable of blocking infection by global viruses has not been achieved, and remains a key public health challenge. Objective: Objective:During infection, a robust strain-specific neutralizing response develops in most people, but only a subset of infected people develop broadly neutralizing antibodies. Understanding how and why these broadly neutralizing antibodies develop has been a focus of the HIV-1 vaccine field for many years, and has generated extraordinary insights into the neutralizing response to HIV-1 infection. Results: This review describes the features, targets and developmental pathways of early strain-specific antibodies and later broadly neutralizing antibodies, and explores the reasons such broad antibodies are not more commonly elicited during infection. Conclusion: The insights from these studies have been harnessed for the development of pioneering new vaccine approaches that seek to drive B cell maturation towards breadth. Overall, this review describes how findings from infected donors have impacted on active and passive immunization approaches that seek to prevent HIV-1 infection.

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Section: Broadly Neutralizing Antibodiesmentioning

confidence: 99%

The Neutralizing Antibody Response to the HIV-1 Env Protein

Moore

2018

CHR

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“…As the only viral protein on the surface of HIV-1 virions, Env trimer is the sole target of neutralizing antibodies that prevent infection of host cells (McCoy and Burton, 2017). …”

Section: Introductionmentioning

confidence: 99%

Asymmetric recognition of HIV-1 Envelope trimer by V1V2 loop-targeting antibodies

Wang

Gristick

Scharf

et al. 2017

eLife

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The HIV-1 envelope (Env) glycoprotein binds to host cell receptors to mediate membrane fusion. The prefusion Env trimer is stabilized by V1V2 loops that interact at the trimer apex. Broadly neutralizing antibodies (bNAbs) against V1V2 loops, exemplified by PG9, bind asymmetrically as a single Fab to the apex of the symmetric Env trimer using a protruding CDRH3 to penetrate the Env glycan shield. Here we characterized a distinct mode of V1V2 epitope recognition by the new bNAb BG1 in which two Fabs bind asymmetrically per Env trimer using a compact CDRH3. Comparisons between cryo-EM structures of Env trimer complexed with BG1 (6.2 Å resolution) and PG9 (11.5 Å resolution) revealed a new V1V2-targeting strategy by BG1. Analyses of the EM structures provided information relevant to vaccine design including molecular details for different modes of asymmetric recognition of Env trimer and a binding model for BG1 recognition of V1V2 involving glycan flexibility.DOI: http://dx.doi.org/10.7554/eLife.27389.001

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“…They further contribute to protein folding, interact with host cell receptors such as DC-SIGN and are indispensable for viral infectivity [5–7]. The majority of Env-targeting bNAbs incorporate glycans into their epitopes [8], which highlights the importance of the glycans to be considered and included in rational immunogen design [9,10]. The particularly dense glycans impose steric constraints on early glycan trimming enzymes i.e.…”

Section: The Extensively Glycosylated Viral Spike Is the Focus Of mentioning

confidence: 99%

Glycosylation profiling to evaluate glycoprotein immunogens against HIV-1

Behrens

Struwe

Crispin

2017

Expert Review of Proteomics

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Introduction Much of the efforts to develop a vaccine against the human immunodeficiency virus (HIV) have focused on the design of recombinant mimics of the viral attachment glycoprotein (Env). The leading immunogens exhibit native-like antigenic properties and are being investigated for their ability to induce broadly neutralizing antibodies (bNAbs). Understanding the relative abundance of glycans at particular glycosylation sites on these immunogens is important as most bNAbs have evolved to recognize or evade the dense coat of glycans that masks much of the protein surface. Understanding the glycan structures on candidate immunogens enables triaging between native-like conformations and immunogens lacking key structural features as steric constraints limit glycan processing. The sensitivity of the processing state of a particular glycan to its structural environment has led to the need for quantitative glycan profiling and site-specific analysis to probe the structural integrity of immunogens. Areas covered We review analytical methodologies for HIV immunogen evaluation and discuss how these studies have led to a greater understanding of the structural constraints that control the glycosylation state of the HIV attachment and fusion spike. Expert commentary Total composition and site-specific glycosylation profiling are emerging as standard methods in the evaluation of Env-based immunogen candidates.

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Identification and specificity of broadly neutralizing antibodies against HIV

Cited by 210 publications

References 105 publications

The Neutralizing Antibody Response to the HIV-1 Env Protein

The Neutralizing Antibody Response to the HIV-1 Env Protein

Asymmetric recognition of HIV-1 Envelope trimer by V1V2 loop-targeting antibodies

Glycosylation profiling to evaluate glycoprotein immunogens against HIV-1

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