Microbiology & Immunology - Research Publications

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    What Lies Beneath: Antibody Dependent Natural Killer Cell Activation by Antibodies to Internal Influenza Virus Proteins
    Vanderven, HA ; Ana-Sosa-Batiz, F ; Jegaskanda, S ; Rockman, S ; Laurie, K ; Barr, I ; Chen, W ; Wines, B ; Hogarth, PM ; Lambe, T ; Gilbert, SC ; Parsons, MS ; Kent, SJ (ELSEVIER SCIENCE BV, 2016-06)
    The conserved internal influenza proteins nucleoprotein (NP) and matrix 1 (M1) are well characterised for T cell immunity, but whether they also elicit functional antibodies capable of activating natural killer (NK) cells has not been explored. We studied NP and M1-specific ADCC activity using biochemical, NK cell activation and killing assays with plasma from healthy and influenza-infected subjects. Healthy adults had antibodies to M1 and NP capable of binding dimeric FcγRIIIa and activating NK cells. Natural symptomatic and experimental influenza infections resulted in a rise in antibody dependent NK cell activation post-infection to the hemagglutinin of the infecting strain, but changes in NK cell activation to M1 and NP were variable. Although antibody dependent killing of target cells infected with vaccinia viruses expressing internal influenza proteins was not detected, opsonising antibodies to NP and M1 likely contribute to an antiviral microenvironment by stimulating innate immune cells to secrete cytokines early in infection. We conclude that effector cell activating antibodies to conserved internal influenza proteins are common in healthy and influenza-infected adults. Given the significance of such antibodies in animal models of heterologous influenza infection, the definition of their importance and mechanism of action in human immunity to influenza is essential.
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    Seminal Plasma Anti-HIV Antibodies Trigger Antibody-dependent Cellular Cytotoxicity: Implications for HIV Transmission
    Parsons, MS ; Madhavi, V ; Ana-Sosa-Batiz, F ; Center, RJ ; Wilson, KM ; Bunupuradah, T ; Ruxrungtham, K ; Kent, SJ (LIPPINCOTT WILLIAMS & WILKINS, 2016-01-01)
    Recent evidence from HIV vaccine trials in humans and non-human primates suggests that nonneutralizing antibody functions, such as antibody-dependent cellular cytotoxicity (ADCC), are an important component of vaccine-mediated protection. Whether anti-HIV ADCC antibodies are present in seminal fluid, however, is not known. We assessed whether anti-HIV antibodies within seminal plasma mediate ADCC and activate natural killer (NK) cells. Using matched blood and seminal plasma samples, we detected anti-HIV IgG within samples from all 11 HIV-infected donors. Furthermore, anti-HIV antibodies within the seminal plasma triggered detectable ADCC in 9 of 11 donors and activated NK cells in 6 of 11 donors. The ability of seminal plasma-derived IgG to activate NK cells in an anti-HIV antibody-dependent manner was enhanced when IgG were enriched and other seminal plasma components were removed. These observations have relevance for understanding natural immunity to HIV infection and provide assistance with HIV vaccine design.