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- Title
Antibody-Dependent Natural Killer Cell Activation After Ebola Vaccination.
- Authors
Wagstaffe, Helen R; Clutterbuck, Elizabeth A; Bockstal, Viki; Stoop, Jeroen N; Luhn, Kerstin; Douoguih, Macaya; Shukarev, Georgi; Snape, Matthew D; Pollard, Andrew J; Riley, Eleanor M; Goodier, Martin R
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
UNITED Kingdom; KILLER cells; ANTIBODY-dependent cell cytotoxicity; EBOLA virus disease; VACCINATION; EBOLA virus; CONTACT tracing; EBOLA virus disease prevention; PROTEINS; RESEARCH; VIRAL vaccines; IMMUNIZATION; RESEARCH methodology; EVALUATION research; COMPARATIVE studies; IMMUNITY; GLYCOPROTEINS; RESEARCH funding; VIRAL antibodies
- Publication
Journal of Infectious Diseases, 2021, Vol 223, Issue 7, p1171
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiz657