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Fc receptor-mediated phagocytosis in tissues as a potent mechanism for preventive and therapeutic HIV vaccine strategies

(2016) MUCOSAL IMMUNOLOGY. 9(6). p.1584-1595
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Abstract
Although the development of a fully protective HIV vaccine is the ultimate goal of HIV research, to date only one HIV vaccine trial, the RV144, has successfully induced a weakly protective response. The 31% protection from infection achieved in the RV144 trial was linked to the induction of nonneutralizing antibodies, able to mediate antibody-dependent cell-mediated cytotoxicity (ADCC), suggestive of an important role of Fc-mediated functions in protection. Similarly, Fc-mediated antiviral activity was recently shown to play a critical role in actively suppressing the viral reservoir, but the Fc effector mechanisms within tissues that provide protection from or after infection are largely unknown. Here we aimed to define the landscape of effector cells and Fc receptors present within vulnerable tissues. We found negligible Fc receptor-expressing natural killer cells in the female reproductive and gastrointestinal mucosa. Conversely, Fc receptor-expressing macrophages were highly enriched in most tissues, but neutrophils mediated superior antibody-mediated phagocytosis. Modifications in Fc domain of VRC01 antibody increased phagocytic responses in both phagocytes. These data suggest that non-ADCC-mediated mechanisms, such as phagocytosis and neutrophil activation, are more likely to play a role in preventative vaccine or reservoir-eliminating therapeutic approaches.
Keywords
HUMAN-IMMUNODEFICIENCY-VIRUS, BROADLY NEUTRALIZING ANTIBODIES, MONOCYTE-DERIVED MACROPHAGES, MUCOSAL SHIV CHALLENGE, IN-VIVO, MONOCLONAL-ANTIBODY, EFFECTOR FUNCTIONS, ANTIRETROVIRAL THERAPY, INFECTED PATIENTS, RHESUS-MONKEYS

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Chicago
Sips, Magdalena, M Krykbaeva, TJ Diefenbach, M Ghebremichael, BA Bowman, A-S Dugast, AW Boesch, et al. 2016. “Fc Receptor-mediated Phagocytosis in Tissues as a Potent Mechanism for Preventive and Therapeutic HIV Vaccine Strategies.” Mucosal Immunology 9 (6): 1584–1595.
APA
Sips, M., Krykbaeva, M., Diefenbach, T., Ghebremichael, M., Bowman, B., Dugast, A.-S., Boesch, A., et al. (2016). Fc receptor-mediated phagocytosis in tissues as a potent mechanism for preventive and therapeutic HIV vaccine strategies. MUCOSAL IMMUNOLOGY, 9(6), 1584–1595.
Vancouver
1.
Sips M, Krykbaeva M, Diefenbach T, Ghebremichael M, Bowman B, Dugast A-S, et al. Fc receptor-mediated phagocytosis in tissues as a potent mechanism for preventive and therapeutic HIV vaccine strategies. MUCOSAL IMMUNOLOGY. 2016;9(6):1584–95.
MLA
Sips, Magdalena et al. “Fc Receptor-mediated Phagocytosis in Tissues as a Potent Mechanism for Preventive and Therapeutic HIV Vaccine Strategies.” MUCOSAL IMMUNOLOGY 9.6 (2016): 1584–1595. Print.
@article{8173497,
  abstract     = {Although the development of a fully protective HIV vaccine is the ultimate goal of HIV research, to date only one HIV vaccine trial, the RV144, has successfully induced a weakly protective response. The 31% protection from infection achieved in the RV144 trial was linked to the induction of nonneutralizing antibodies, able to mediate antibody-dependent cell-mediated cytotoxicity (ADCC), suggestive of an important role of Fc-mediated functions in protection. Similarly, Fc-mediated antiviral activity was recently shown to play a critical role in actively suppressing the viral reservoir, but the Fc effector mechanisms within tissues that provide protection from or after infection are largely unknown. Here we aimed to define the landscape of effector cells and Fc receptors present within vulnerable tissues. We found negligible Fc receptor-expressing natural killer cells in the female reproductive and gastrointestinal mucosa. Conversely, Fc receptor-expressing macrophages were highly enriched in most tissues, but neutrophils mediated superior antibody-mediated phagocytosis. Modifications in Fc domain of VRC01 antibody increased phagocytic responses in both phagocytes. These data suggest that non-ADCC-mediated mechanisms, such as phagocytosis and neutrophil activation, are more likely to play a role in preventative vaccine or reservoir-eliminating therapeutic approaches.},
  author       = {Sips, Magdalena and Krykbaeva, M and Diefenbach, TJ and Ghebremichael, M and Bowman, BA and Dugast, A-S and Boesch, AW and Streeck, H and Kwon, DS and Ackerman, ME and Suscovich, TJ and Brouckaert, Peter and Schacker, TW and Alter, G},
  issn         = {1933-0219},
  journal      = {MUCOSAL IMMUNOLOGY},
  keywords     = {HUMAN-IMMUNODEFICIENCY-VIRUS,BROADLY NEUTRALIZING ANTIBODIES,MONOCYTE-DERIVED MACROPHAGES,MUCOSAL SHIV CHALLENGE,IN-VIVO,MONOCLONAL-ANTIBODY,EFFECTOR FUNCTIONS,ANTIRETROVIRAL THERAPY,INFECTED PATIENTS,RHESUS-MONKEYS},
  language     = {eng},
  number       = {6},
  pages        = {1584--1595},
  title        = {Fc receptor-mediated phagocytosis in tissues as a potent mechanism for preventive and therapeutic HIV vaccine strategies},
  url          = {http://dx.doi.org/10.1038/mi.2016.12},
  volume       = {9},
  year         = {2016},
}

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