Antibody-dependent natural killer cell activation after Ebola vaccination

<p><strong>Background</strong></p> <p>Antibody Fc-mediated functions, such as antibody-dependent cellular cytotoxicity, contribute to vaccine-induced protection against viral infections. Fc-mediated function of anti-Ebola glycoprotein (GP) antibodies suggest that Fc-dep...

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Main Authors: Wagstaffe, HR, Clutterbuck, EA, Bockstal, V, Stoop, JN, Luhn, K, Douoguih, M, Shukarev, G, Snape, MD, Pollard, AJ, Riley, EM, Goodier, MR
Format: Journal article
Language:English
Published: Oxford University Press 2019
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author Wagstaffe, HR
Clutterbuck, EA
Bockstal, V
Stoop, JN
Luhn, K
Douoguih, M
Shukarev, G
Snape, MD
Pollard, AJ
Riley, EM
Goodier, MR
author_facet Wagstaffe, HR
Clutterbuck, EA
Bockstal, V
Stoop, JN
Luhn, K
Douoguih, M
Shukarev, G
Snape, MD
Pollard, AJ
Riley, EM
Goodier, MR
author_sort Wagstaffe, HR
collection OXFORD
description <p><strong>Background</strong></p> <p>Antibody Fc-mediated functions, such as antibody-dependent cellular cytotoxicity, contribute to vaccine-induced protection against viral infections. Fc-mediated function of anti-Ebola glycoprotein (GP) antibodies suggest that Fc-dependent activation of effector cells, including natural killer (NK) cells, could play a role in vaccination against Ebola virus disease.</p> <p><strong>Methods</strong></p> <p>We analyzed the effect on primary human NK cell activation of anti-Ebola GP antibody in the serum of United Kingdom–based volunteers vaccinated with the novel 2-dose heterologous adenovirus type 26.ZEBOV, modified vaccinia Ankara–BN-Filo vaccine regimen.</p> <p><strong>Results</strong></p> <p>We demonstrate primary human NK cell CD107a and interferon γ expression, combined with down-regulation of CD16, in response to recombinant Ebola virus GP and post-vaccine dose 1 and dose 2 serum samples. These responses varied significantly with vaccine regimen, and NK cell activation was found to correlate with anti-GP antibody concentration. We also reveal an impact of NK cell differentiation phenotype on antibody-dependent NK cell activation, with highly differentiated CD56dimCD57+ NK cells being the most responsive.</p> <p><strong>Conclusions</strong></p> <p>These findings highlight the dual importance of vaccine-induced antibody concentration and NK cell differentiation status in promoting Fc-mediated activation of NK cells after vaccination, raising a potential role for antibody-mediated NK cell activation in vaccine-induced immune responses.</p>
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spelling oxford-uuid:afacdaff-8db2-4f85-8948-189cf947a25e2022-03-27T03:51:03ZAntibody-dependent natural killer cell activation after Ebola vaccinationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:afacdaff-8db2-4f85-8948-189cf947a25eEnglishSymplectic Elements at OxfordOxford University Press2019Wagstaffe, HRClutterbuck, EABockstal, VStoop, JNLuhn, KDouoguih, MShukarev, GSnape, MDPollard, AJRiley, EMGoodier, MR<p><strong>Background</strong></p> <p>Antibody Fc-mediated functions, such as antibody-dependent cellular cytotoxicity, contribute to vaccine-induced protection against viral infections. Fc-mediated function of anti-Ebola glycoprotein (GP) antibodies suggest that Fc-dependent activation of effector cells, including natural killer (NK) cells, could play a role in vaccination against Ebola virus disease.</p> <p><strong>Methods</strong></p> <p>We analyzed the effect on primary human NK cell activation of anti-Ebola GP antibody in the serum of United Kingdom–based volunteers vaccinated with the novel 2-dose heterologous adenovirus type 26.ZEBOV, modified vaccinia Ankara–BN-Filo vaccine regimen.</p> <p><strong>Results</strong></p> <p>We demonstrate primary human NK cell CD107a and interferon γ expression, combined with down-regulation of CD16, in response to recombinant Ebola virus GP and post-vaccine dose 1 and dose 2 serum samples. These responses varied significantly with vaccine regimen, and NK cell activation was found to correlate with anti-GP antibody concentration. We also reveal an impact of NK cell differentiation phenotype on antibody-dependent NK cell activation, with highly differentiated CD56dimCD57+ NK cells being the most responsive.</p> <p><strong>Conclusions</strong></p> <p>These findings highlight the dual importance of vaccine-induced antibody concentration and NK cell differentiation status in promoting Fc-mediated activation of NK cells after vaccination, raising a potential role for antibody-mediated NK cell activation in vaccine-induced immune responses.</p>
spellingShingle Wagstaffe, HR
Clutterbuck, EA
Bockstal, V
Stoop, JN
Luhn, K
Douoguih, M
Shukarev, G
Snape, MD
Pollard, AJ
Riley, EM
Goodier, MR
Antibody-dependent natural killer cell activation after Ebola vaccination
title Antibody-dependent natural killer cell activation after Ebola vaccination
title_full Antibody-dependent natural killer cell activation after Ebola vaccination
title_fullStr Antibody-dependent natural killer cell activation after Ebola vaccination
title_full_unstemmed Antibody-dependent natural killer cell activation after Ebola vaccination
title_short Antibody-dependent natural killer cell activation after Ebola vaccination
title_sort antibody dependent natural killer cell activation after ebola vaccination
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