Update on Fc-Mediated Antibody Functions Against HIV-1 Beyond Neutralization

Su, Bin; Dispinseri, Stefania; Iannone, Valeria; Zhang, Tong; Wu, Hao; Carapito, Raphaël; Bahram, Seiamak; Scarlatti, Gabriella; Moog, Christiane

doi:10.3389/fimmu.2019.02968

Cited by 49 publications

(54 citation statements)

References 201 publications

(218 reference statements)

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“…How close antigens are to each other, as well as their individual size and shape, could influence how Fc domains are presented as well as the level of avidity experienced ( Figure 11A). There is some evidence to suggest that where an antibody binds on antigen may influence innate effector activity for HIV (261), influenza (262,263) and Ebola viruses (104,264), among other examples, but there is not yet convincing molecular data to provide a general model that ties these observations together.…”

Section: Reconciling Antibody-antigen and Antibody-fcγr Structuresmentioning

confidence: 99%

Considerations of Antibody Geometric Constraints on NK Cell Antibody Dependent Cellular Cytotoxicity

Murin

2020

Front. Immunol.

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It has been well-established that antibody isotype, glycosylation, and epitope all play roles in the process of antibody dependent cellular cytotoxicity (ADCC). For natural killer (NK) cells, these phenotypes are linked to cellular activation through interaction with the IgG receptor FcγRIIIa, a single pass transmembrane receptor that participates in cytoplasmic signaling complexes. Therefore, it has been hypothesized that there may be underlying spatial and geometric principles that guide proper assembly of an activation complex within the NK cell immune synapse. Further, synergy of antibody phenotypic properties as well as allosteric changes upon antigen binding may also play an as-of-yet unknown role in ADCC. Understanding these facets, however, remains hampered by difficulties associated with studying immune synapse dynamics using classical approaches. In this review, I will discuss relevant NK cell biology related to ADCC, including the structural biology of Fc gamma receptors, and how the dynamics of the NK cell immune synapse are being studied using innovative microscopy techniques. I will provide examples from the literature demonstrating the effects of spatial and geometric constraints on the T cell receptor complex and how this relates to intracellular signaling and the molecular nature of lymphocyte activation complexes, including those of NK cells. Finally, I will examine how the integration of high-throughput and "omics" technologies will influence basic NK cell biology research moving forward. Overall, the goal of this review is to lay a basis for understanding the development of drugs and therapeutic antibodies aimed at augmenting appropriate NK cell ADCC activity in patients being treated for a wide range of illnesses.

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Section: Reconciling Antibody-antigen and Antibody-fcγr Structuresmentioning

confidence: 99%

Considerations of Antibody Geometric Constraints on NK Cell Antibody Dependent Cellular Cytotoxicity

Murin

2020

Front. Immunol.

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“…This is in contrast to fields where vaccines are used to treat infectious disease. In these contexts, it is well-acknowledged that antibody subclass plays an active role in controlling viral infections (66)(67)(68). One posited role for this effect is the engagement of additional activating Fc Receptors in myeloid cell populations (56).…”

Section: Discussionmentioning

confidence: 99%

Multifactorial Design of a Supramolecular Peptide Anti-IL-17 Vaccine Toward the Treatment of Psoriasis

et al. 2020

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Current treatments for chronic immune-mediated diseases such as psoriasis, rheumatoid arthritis, or Crohn's disease commonly rely on cytokine neutralization using monoclonal antibodies; however, such approaches have drawbacks. Frequent repeated dosing can lead to the formation of anti-drug antibodies and patient compliance issues, and it is difficult to identify a single antibody that is broadly efficacious across diverse patient populations. As an alternative to monoclonal antibody therapy, anti-cytokine immunization is a potential means for long-term therapeutic control of chronic inflammatory diseases. Here we report a supramolecular peptide-based approach for raising antibodies against IL-17 and demonstrate its efficacy in a murine model of psoriasis. B-cell epitopes from IL-17 were co-assembled with the universal T-cell epitope PADRE using the Q11 self-assembling peptide nanofiber system. These materials, with or without adjuvants, raised antibody responses against IL-17. Exploiting the modularity of the system, multifactorial experimental designs were used to select formulations maximizing titer and avidity. In a mouse model of psoriasis induced by imiquimod, unadjuvanted nanofibers had therapeutic efficacy, which could be enhanced with alum adjuvant but reversed with CpG adjuvant. Measurements of antibody subclass induced by adjuvanted and unadjuvanted formulations revealed strong correlations between therapeutic efficacy and titers of IgG1 (improved efficacy) or IgG2b (worsened efficacy). These findings have important implications for the development of anti-cytokine active immunotherapies and suggest that immune phenotype is an important metric for eliciting therapeutic anti-cytokine antibody responses.

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“…The cross-linkage among the antigen, antibody and the effector cells triggers immune effector functions, including antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP) and complement-dependent cytotoxicity (CDC), which contribute to the clearance of virus-infected cells and virus particles (ADCP particularly) ( Figure 2 C). Many sources of evidence have shown that effector functions mediated by antibodies are critical for protection against influenza virus, human immunodeficiency virus and respiratory syncytial virus [ 117 , 118 , 119 ]. In addition, ADCC antibodies are associated with the clinical presentation of neonatal herpes simplex virus (HSV) infection [ 120 ] and are protective against HSV-1 and -2 in a mouse model of maternal immunization [ 121 ].…”

Section: Mda Interference: a Major Bottleneck For Ndv-vectored Vacmentioning

confidence: 99%

Newcastle Disease Virus as a Vaccine Vector for 20 Years: A Focus on Maternally Derived Antibody Interference

Cao

et al. 2020

Vaccines

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It has been 20 years since Newcastle disease virus (NDV) was first used as a vector. The past two decades have witnessed remarkable progress in vaccine generation based on the NDV vector and optimization of the vector. Protective antigens of a variety of pathogens have been expressed in the NDV vector to generate novel vaccines for animals and humans, highlighting a great potential of NDV as a vaccine vector. More importantly, the research work also unveils a major problem restraining the NDV vector vaccines in poultry, i.e., the interference from maternally derived antibody (MDA). Although many efforts have been taken to overcome MDA interference, a lack of understanding of the mechanism of vaccination inhibition by MDA in poultry still hinders vaccine improvement. In this review, we outline the history of NDV as a vaccine vector by highlighting some milestones. The recent advances in the development of NDV-vectored vaccines or therapeutics for animals and humans are discussed. Particularly, we focus on the mechanisms and hypotheses of vaccination inhibition by MDA and the efforts to circumvent MDA interference with the NDV vector vaccines. Perspectives to fill the gap of understanding concerning the mechanism of MDA interference in poultry and to improve the NDV vector vaccines are also proposed.

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Update on Fc-Mediated Antibody Functions Against HIV-1 Beyond Neutralization

Cited by 49 publications

References 201 publications

Considerations of Antibody Geometric Constraints on NK Cell Antibody Dependent Cellular Cytotoxicity

Considerations of Antibody Geometric Constraints on NK Cell Antibody Dependent Cellular Cytotoxicity

Multifactorial Design of a Supramolecular Peptide Anti-IL-17 Vaccine Toward the Treatment of Psoriasis

Newcastle Disease Virus as a Vaccine Vector for 20 Years: A Focus on Maternally Derived Antibody Interference

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