Epitope specificity plays a critical role in regulating antibody-dependent cell-mediated cytotoxicity against influenza A virus
Wenqian He,Gene S. Tan,Caitlin E. Mullarkey,Amanda J. Lee,Mannie Man Wai Lam,Florian Krammer,Carole Henry,Patrick C. Wilson,Ali A. Ashkar,Peter Palese,Matthew S. Miller +10 more
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The data demonstrate that antibody specificity plays an important role in the regulation of ADCC, and that cross-talk among antibodies of varying specificities determines the magnitude of Fc receptor-mediated effector functions.Abstract:
The generation of strain-specific neutralizing antibodies against influenza A virus is known to confer potent protection against homologous infections. The majority of these antibodies bind to the hemagglutinin (HA) head domain and function by blocking the receptor binding site, preventing infection of host cells. Recently, elicitation of broadly neutralizing antibodies which target the conserved HA stalk domain has become a promising “universal” influenza virus vaccine strategy. The ability of these antibodies to elicit Fc-dependent effector functions has emerged as an important mechanism through which protection is achieved in vivo. However, the way in which Fc-dependent effector functions are regulated by polyclonal influenza virus-binding antibody mixtures in vivo has never been defined. Here, we demonstrate that interactions among viral glycoprotein-binding antibodies of varying specificities regulate the magnitude of antibody-dependent cell-mediated cytotoxicity induction. We show that the mechanism responsible for this phenotype relies upon competition for binding to HA on the surface of infected cells and virus particles. Nonneutralizing antibodies were poor inducers and did not inhibit antibody-dependent cell-mediated cytotoxicity. Interestingly, anti-neuraminidase antibodies weakly induced antibody-dependent cell-mediated cytotoxicity and enhanced induction in the presence of HA stalk-binding antibodies in an additive manner. Our data demonstrate that antibody specificity plays an important role in the regulation of ADCC, and that cross-talk among antibodies of varying specificities determines the magnitude of Fc receptor-mediated effector functions.read more
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Beyond binding: antibody effector functions in infectious diseases.
TL;DR: Antibodies play an essential role in host defence against pathogens by recognizing microorganisms or infected cells as mentioned in this paper, and they can control and eradicate infections through a variety of other mechanisms.
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The role of IgG Fc receptors in antibody-dependent enhancement.
TL;DR: The history of the ADE phenomenon is explored, the diversity of immune responses mediated upon FcγR engagement is discussed and the available experimental evidence supporting the role of F cγRs in antiviral protection and pathogenesis through ADE is reviewed.
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Fc-Mediated Antibody Effector Functions During Respiratory Syncytial Virus Infection and Disease.
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Florian Krammer,Florian Krammer,Ron A. M. Fouchier,Ron A. M. Fouchier,Maryna C. Eichelberger,Richard J. Webby,Kathryn Shaw-Saliba,Hongquan Wan,Patrick C. Wilson,Richard W. Compans,Ioanna Skountzou,Arnold S. Monto +11 more
TL;DR: Open questions and knowledge gaps that have been identified by a neuraminidase focus group are reviewed and how the gaps can be addressed are discussed, with the ultimate goal of designing better influenza virus vaccines.
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Antitumor Benefits of Antiviral Immunity: An Underappreciated Aspect of Oncolytic Virotherapies
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References
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Jens Wrammert,Dimitrios G. Koutsonanos,Gui-Mei Li,Srilatha Edupuganti,Jianhua Sui,Michael Morrissey,Megan McCausland,Ioanna Skountzou,Mady Hornig,W. Ian Lipkin,Aneesh K. Mehta,Behzad Razavi,Carlos del Rio,Nai-Ying Zheng,Jane-Hwei Lee,Min Huang,Zahida Ali,Kaval Kaur,Sarah F. Andrews,Rama Rao Amara,Youliang Wang,Suman R. Das,Christopher D. O'Donnell,J W Yewdell,Kanta Subbarao,Wayne A. Marasco,Mark J. Mulligan,Richard W. Compans,Rafi Ahmed,Patrick C. Wilson +29 more
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Journal ArticleDOI
Broadly neutralizing hemagglutinin stalk–specific antibodies require FcγR interactions for protection against influenza virus in vivo
TL;DR: DiLillo et al. as mentioned in this paper showed that anti-stalk mAbs can mediate antibody-dependent cell cytotoxicity and require interactions with Fc receptors for their in vivo neutralizing activity.
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