NK cell subset redistribution and antibody dependent activation after Ebola vaccination in Africans
Author(s)
Type
Journal Article
Abstract
Natural killer cells play an important role in the control of viral infections both by regulating acquired immune responses and as potent innate or antibody-mediated cytotoxic effector cells. NK cells have been implicated in control of Ebola virus infections and our previous studies in European trial participants have demonstrated durable activation, proliferation and antibody-dependent NK cell activation after heterologous two-dose Ebola vaccination with adenovirus type 26.ZEBOV followed by modified vaccinia Ankara-BN-Filo. Regional variation in immunity and environmental exposure to pathogens, in particular human cytomegalovirus, have profound impacts on NK cell functional capacity. We therefore assessed the NK cell phenotype and function in African trial participants with universal exposure to HCMV. We demonstrate a significant redistribution of NK cell subsets after vaccine dose two, involving the enrichment of less differentiated CD56dimCD57− and CD56dimFcεR1γ+ (canonical) cells and the increased proliferation of these subsets. Sera taken after vaccine dose two support robust antibody-dependent NK cell activation in a standard NK cell readout; these responses correlate strongly with the concentration of anti-Ebola glycoprotein specific antibodies. These sera also promote comparable IFN-γ production in autologous NK cells taken at baseline and post-vaccine dose two. However, degranulation responses of post-vaccination NK cells were reduced compared to baseline NK cells and these effects could not be directly attributed to alterations in NK cell phenotype after vaccination. These studies demonstrate consistent changes in NK cell phenotypic composition and robust antibody-dependent NK cell function and reveal novel characteristics of these responses after heterologous two dose Ebola vaccination in African individuals
Date Issued
2022-06-01
Online Publication Date
2022-07-06T13:58:37Z
Date Acceptance
2022-05-27
ISSN
2076-393X
Publisher
MDPI AG
Journal / Book Title
Vaccines
Volume
10
Issue
6
Copyright Statement
©2022 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
License URI
Identifier
https://www.mdpi.com/2076-393X/10/6/884
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000816099500001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
Medicine, Research & Experimental
Research & Experimental Medicine
Ebola
vaccine
natural killer cell
antibody
Africa
HUMAN CYTOMEGALOVIRUS CMV
H1N1 INFLUENZA VACCINE
INFECTION
RESPONSES
DIFFERENTIATION
PROTECTION
COCKTAIL
IMPACT
Africa
Ebola
antibody
natural killer cell
vaccine
Science & Technology
Life Sciences & Biomedicine
Immunology
Medicine, Research & Experimental
Research & Experimental Medicine
Ebola
vaccine
natural killer cell
antibody
Africa
HUMAN CYTOMEGALOVIRUS CMV
H1N1 INFLUENZA VACCINE
INFECTION
RESPONSES
DIFFERENTIATION
PROTECTION
COCKTAIL
IMPACT
Publication Status
Published
Article Number
ARTN 884