ORCID Profile
0000-0001-8482-2308
Current Organisation
James Cook University
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Publisher: Oxford University Press (OUP)
Date: 02-09-2022
DOI: 10.1093/CEI/UXAC082
Abstract: Natural killer (NK) cells are important anti-viral effector cells. The function and phenotype of the NK cells that constitute an in idual’s NK cell repertoire can be influenced by ongoing or previous viral infections. Indeed, infection with human cytomegalovirus (HCMV) drives the expansion of a highly differentiated NK cell population characterized by expression of CD57 and the activating NKG2C receptor. This NK cell population has also been noted to occur in HIV-1-infected in iduals. We evaluated the NK cells of HIV-1-infected and HIV-1-uninfected in iduals to determine the relative frequency of highly differentiated CD57+NKG2C+ NK cells and characterize these cells for their receptor expression and responsiveness to erse stimuli. Highly differentiated CD57+NKG2C+ NK cells occurred at higher frequencies in HCMV-infected donors relative to HCMV-uninfected donors and were dramatically expanded in HIV-1/HCMV co-infected donors. The expanded CD57+NKG2C+ NK cell population in HIV-1-infected donors remained stable following antiretroviral therapy. CD57+NKG2C+ NK cells derived from HIV-1-infected in iduals were robustly activated by antibody-dependent stimuli that contained anti-HIV-1 antibodies or therapeutic anti-CD20 antibody, and these NK cells mediated cytolysis through NKG2C. Lastly, CD57+NKG2C+ NK cells from HIV-1-infected donors were characterized by reduced expression of the inhibitory NKG2A receptor. The abundance of highly functional CD57+NKG2C+ NK cells in HIV-1-infected in iduals raises the possibility that these NK cells could play a role in HIV-1 pathogenesis or serve as effector cells for therapeutic/cure strategies.
Publisher: American Society for Clinical Investigation
Date: 06-07-2017
Publisher: Public Library of Science (PLoS)
Date: 28-04-2016
Publisher: Elsevier BV
Date: 06-2016
Publisher: Elsevier BV
Date: 07-2012
Publisher: Elsevier BV
Date: 05-2019
Publisher: American Society for Microbiology
Date: 03-2019
DOI: 10.1128/JVI.02090-18
Abstract: Protection from severe influenza may be assisted by antibodies that engage NK cells to kill infected cells through ADCC. Studies have primarily focused on antibodies that have ADCC activity, rather than the capacity of NK cells to become activated and mediate ADCC during an influenza virus infection. We found that type I interferon released in response to influenza virus infection primes NK cells to become highly reactive to anti-influenza virus ADCC antibodies. Enhancing the capacity of NK cells to mediate ADCC could assist in controlling influenza virus infections.
Publisher: Oxford University Press (OUP)
Date: 02-11-2018
Abstract: Older adults are at high risk of influenza disease, but generally respond poorly to vaccination. Antibody-dependent cellular cytotoxicity (ADCC) may be an important component of protection against influenza infection. An improved understanding of the ADCC response to influenza vaccination in older adults is required. We studied sera s les from 3 groups of subjects aged ≥65 years (n = 16-17/group) receiving the 2008/2009 seasonal trivalent influenza vaccine (TIV). Subjects had minimal pre-existing hemagglutination inhibiting (HAI) antibodies and TIV induced either no, low, or high HAI responses. Serum ADCC activity was analyzed using Fc receptor cross-linking, NK cell activation, and influenza-infected cell killing. Most subjects from TIV nonresponder, low responder, and high responder groups had detectable ADCC antibodies prevaccination, but baseline ADCC was not predictive of HAI vaccine responsiveness. Interestingly, ADCC and HAI responses tracked closely across all groups, against all 3 TIV hemagglutinins, and in all ADCC assays tested. Older adults commonly have pre-existing ADCC antibodies in the absence of high HAI titers to circulating influenza strains. In older vaccinees, ADCC response mirrored HAI antibodies and was readily detectable despite high postvaccination HAI titers. Alternate measures of vaccine responsiveness and improved vaccinations in this at-risk group are needed.
Publisher: Wiley
Date: 09-11-2021
DOI: 10.1111/IMCB.12508
Abstract: Humans are exposed to influenza virus through periodic infections. Due to these repeated exposures, human populations commonly have elevated antibody titers targeting the conserved internal influenza virus nucleoprotein (NP). Despite the presence of anti‐NP antibodies, humans are acutely susceptible to drifted influenza viruses with antigenically different surface proteins and the protective potential of human NP antibodies is unclear. In this study, high levels of anti‐NP antibody and NP‐specific B cells were detected in both adult humans and influenza‐infected mice, confirming that NP is a major target of humoral immunity. Through sorting single B cells from influenza‐exposed human adults, we generated a panel of 11 anti‐NP monoclonal antibodies (mAbs). The majority of anti‐NP human mAbs generated were capable of engaging cellular Fc receptors and bound NP on the surface of influenza‐infected cell lines in vitro , suggesting that anti‐NP mAbs have the potential to mediate downstream Fc effector functions such as antibody‐dependent cellular cytotoxicity and antibody‐dependent phagocytosis. However, human anti‐NP mAbs were not protective in vivo when passively transferred into a murine influenza challenge model. Future in vivo studies examining the synergistic effect of anti‐NP mAbs infused with other influenza‐specific mAbs are warranted.
Publisher: American Society for Clinical Investigation
Date: 24-07-2023
Publisher: Elsevier BV
Date: 02-2020
Publisher: Mary Ann Liebert Inc
Date: 11-2016
Publisher: Wiley
Date: 03-02-2020
DOI: 10.1111/IMCB.12312
Abstract: In recent years, there has been a renewed interest in utilizing antibody fragment crystallizable (Fc) functions to prevent and control viral infections. The protective and therapeutic potential of Fc-mediated antibody functions have been assessed for some clinically important human viruses, including HIV, hemorrhagic fever viruses and influenza virus. There is mounting evidence that influenza-specific antibodies with Fc-mediated functions, such as antibody-dependent cellular cytotoxicity and antibody-dependent phagocytosis, can aid in the clearance of influenza virus infection. Recent influenza challenge studies and intravenous immunoglobulin G therapy studies in humans suggest a protective role for Fc effector functions in vivo. Broadly reactive influenza antibodies with Fc-mediated functions are prevalent in the human population and could inform the development of a universally protective influenza vaccine or therapy. In this review, we explore the utility of antibodies with Fc-mediated effector functions against viral infections with a focus on influenza virus.
Publisher: Informa UK Limited
Date: 03-04-2017
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.COVIRO.2016.12.002
Abstract: Antibodies are a key defence against influenza infection and disease, but neutralizing antibodies are often strain-specific and of limited utility against ergent or pandemic viruses. There is now considerable evidence that influenza-specific antibodies with Fc-mediated effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), can assist in the clearance of influenza infection in vitro and in animal models. Further, ADCC-mediating antibodies that recognize a broad array of influenza strains are common in humans, likely as a result of being regularly exposed to influenza infections. The concept that influenza-specific ADCC can assist in the partial control of influenza infections in humans is gaining momentum. This review examines the utility of influenza-specific ADCC antibodies.
Publisher: Frontiers Media SA
Date: 29-03-2019
Publisher: Springer Science and Business Media LLC
Date: 10-07-2018
DOI: 10.1038/S41467-018-04704-9
Abstract: The high rate of antigenic drift in seasonal influenza viruses necessitates frequent changes in vaccine composition. Recent seasonal H3 vaccines do not protect against swine-origin H3N2 variant (H3N2v) strains that recently have caused severe human infections. Here, we report a human V H 1-69 gene-encoded monoclonal antibody (mAb) designated H3v-47 that exhibits potent cross-reactive neutralization activity against human and swine H3N2 viruses that circulated since 1989. The crystal structure and electron microscopy reconstruction of H3v-47 Fab with the H3N2v hemagglutinin (HA) identify a unique epitope spanning the vestigial esterase and receptor-binding subdomains that is distinct from that of any known neutralizing antibody for influenza A H3 viruses. MAb H3v-47 functions largely by blocking viral egress from infected cells. Interestingly, H3v-47 also engages Fcγ receptor and mediates antibody dependent cellular cytotoxicity (ADCC). This newly identified conserved epitope can be used in design of novel immunogens for development of broadly protective H3 vaccines.
Publisher: Massachusetts Medical Society
Date: 05-10-2017
No related grants have been discovered for Hillary Vanderven.