HIV-Specific Antibody Responses in HIV-Infected Patients: From a Monoclonal to a Polyclonal View

Gallerano, Daniela; Cabauatan, Clarissa R.; Sibanda, Elopy; Valenta, Rudolf

doi:10.1159/000438484

Cited by 8 publications

(7 citation statements)

References 165 publications

(232 reference statements)

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“…This was a clear indication that antibodies were (at the time) an under-appreciated effector mechanism of the immune response against HIV, even though the virus can readily escape them. However, recent years have seen accelerating discoveries of broadly neutralizing antibodies (bnAbs), which are capable of neutralizing many different HIV strains [59–61]. These discoveries have led to interest in defining the role of bnAbs and their generation from an early pool of narrow-specificity antibodies [60], spurring many modeling studies [62].…”

Section: Understanding Immune Effector Mechanismsmentioning

confidence: 99%

Modeling the immune response to HIV infection

Conway

Ribeiro

2018

Current Opinion in Systems Biology

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The interplay between immune response and HIV is intensely studied via mathematical modeling, with significant insights but few direct answers. In this short review, we highlight advances and knowledge gaps across different aspects of immunity. In particular, we identify the innate immune response and its role in priming the adaptive response as ripe for modeling. The latter have been the focus of most modeling studies, but we also synthesize key outstanding questions regarding effector mechanisms of cellular immunity and development of broadly neutralizing antibodies. Thus far, most modeling studies aimed to infer general immune mechanisms; we foresee that significant progress will be made next by detailed quantitative fitting of models to data, and prediction of immune responses.

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Section: Understanding Immune Effector Mechanismsmentioning

confidence: 99%

Modeling the immune response to HIV infection

Conway

Ribeiro

2018

Current Opinion in Systems Biology

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“…Most studies have focused on antibodies directed to gp120, the extracellular Env glycoprotein. The envelope transmembrane protein, gp41, which is required for viral entry, is also a target of both neutralizing and non-neutralizing HIV antibodies [20–24]. During the entry process, gp41 undergoes a series of conformational changes that drive viral and host cell membrane fusion, resulting in opportunities for antibodies to recognize different gp41 epitopes at various stages in the process.…”

Section: Introductionmentioning

confidence: 99%

Identification of HIV gp41-specific antibodies that mediate killing of infected cells

et al. 2019

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Antibodies that mediate killing of HIV-infected cells through antibody-dependent cellular cytotoxicity (ADCC) have been implicated in protection from HIV infection and disease progression. Despite these observations, these types of HIV antibodies are understudied compared to neutralizing antibodies. Here we describe four monoclonal antibodies (mAbs) obtained from one individual that target the HIV transmembrane protein, gp41, and mediate ADCC activity. These four mAbs arose from independent B cell lineages suggesting that in this individual, multiple B cell responses were induced by the gp41 antigen. Competition and phage peptide display mapping experiments suggested that two of the mAbs target epitopes in the cysteine loop that are highly conserved and a common target of HIV gp41-specific antibodies. The amino acid sequences that bind these mAbs are overlapping but distinct. The two other mAbs were competed by mAbs that target the C-terminal heptad repeat (CHR) and the fusion peptide proximal region (FPPR) and appear to both target a similar unique conformational epitope. These gp41-specific mAbs mediated killing of infected cells that express high levels of Env due to either pre-treatment with interferon or deletion of vpu to increase levels of BST-2/Tetherin. They also mediate killing of target cells coated with various forms of the gp41 protein, including full-length gp41, gp41 ectodomain or a mimetic of the gp41 stump. Unlike many ADCC mAbs that target HIV gp120, these gp41-mAbs are not dependent on Env structural changes associated with membrane-bound CD4 interaction. Overall, the characterization of these four new mAbs that target gp41 and mediate ADCC provides evidence for diverse gp41 B cell lineages with overlapping but distinct epitopes within an individual. Such antibodies that can target various forms of envelope protein could represent a common response to a relatively conserved HIV epitope for a vaccine.

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“…Wren et al studied about the effect of ADCC on HIV‐1 infection, and they concluded that ADCC could play an important role in prevention and long state control of HIV‐1 progression . Stimulation immune system and remove pathogens is occurred by IgG1 and IgG2a isotypes production especially GM‐CSF as an adjuvant increase serum levels of both IgG1 and IgG2a antibody isotypes as reported by other researchers .…”

Section: Discussionmentioning

confidence: 84%

Granulocyte‐macrophage colony‐stimulating factor, a potent adjuvant for polarization to Th‐17 pattern: an experience on HIV‐1 vaccine model

Mahdavi

Tajik

Ebtekar

et al. 2017

APMIS

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Cytokines are mediators for polarization of immune response in vaccines. Studies show that co-immunization of DNA vaccines with granulocyte-macrophage colony-stimulating factor (GM-CSF) can increase immune responses. Here, experimental mice were immunized with HIV-1 DNA vaccine with GM-CSF and boosted with recombinant vaccine. Lymphocyte proliferation with Brdu and CTL activity, IL-4, IFN-γ, IL-17 cytokines, total antibody, and IgG1 and IgG2a isotypes were assessed with ELISA. Results show that GM-CSF as adjuvant in DNA immunization significantly increased lymphocyte proliferation and IFN-γ cytokines, but CTL response was tiny increased. Also GM-CSF as adjuvant decreased IL-4 cytokine vs mere vaccine group. IL-17 in the group that immunized with mixture of DNA vaccine/GM-CSF was significantly increased vs DNA vaccine group. Result of total antibody shows that GM-CSF increased antibody response in which both IgG1 and IgG2a increased. Overall, results confirmed the beneficial effect of GM-CSF as adjuvant to increase vaccine immunogenicity. The hallmark result of this study was to increase IL-17 cytokine with DNA vaccine/GM-CSF immunized group. This study for the first time provides the evidence of the potency of GM-CSF in the induction of IL-17 in response to a vaccine, which is important for control of infection such as HIV-1.

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HIV-Specific Antibody Responses in HIV-Infected Patients: From a Monoclonal to a Polyclonal View

Cited by 8 publications

References 165 publications

Modeling the immune response to HIV infection

Modeling the immune response to HIV infection

Identification of HIV gp41-specific antibodies that mediate killing of infected cells

Granulocyte‐macrophage colony‐stimulating factor, a potent adjuvant for polarization to Th‐17 pattern: an experience on HIV‐1 vaccine model

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