Abstract
Influenza vaccination often results in a large percentage of low responders, especially in high-risk groups. As a first line of defense, natural killer (NK) cells play a crucial role in the fight against infections. However, their implication with regard to vaccine responsiveness is insufficiently assessed. Therefore, this study aimed at the validation of essential NK cell features potentially associated with differential vaccine responsiveness with a special focus on NKG2C- and/or CD57-expressing NK cells considered to harbor memory-like functions. To this end, 16 healthy volunteers were vaccinated with an adjuvanted pandemic influenza vaccine. Vaccine responders and low responders were classified according to their hemagglutination inhibition antibody titers. A majority of responders displayed enhanced frequencies of NKG2C-expressing NK cells 7- or 14-days post-vaccination as compared to low responders, whereas the expression of CD57 was not differentially modulated. The NK cell cytotoxic potential was found to be confined to CD56dimCD16+ NKG2C-expressing NK cells in the responders but not in the low responders, which was further confirmed by stochastic neighbor embedding analysis. The presented study is the first of its kind that ascribes CD56dimCD16+ NKG2C-expressing NK cells a crucial role in biasing adaptive immune responses upon influenza vaccination and suggests NKG2C as a potential biomarker in predicting pandemic influenza vaccine responsiveness.
Highlights
Acute respiratory infections caused by the influenza virus are one of the major public health problems leading to high mortality rates worldwide, and to a large societal economic burden [1]
natural killer (NK) cells represent an innate immune cell population that acts as a first line of defense by killing viral infected cells and regulating cells of the adaptive immune system by means of secreted cytokines
This renders NK cells as promising immune players to be considered for the development of vaccination strategies against viral pathogens
Summary
Acute respiratory infections caused by the influenza virus are one of the major public health problems leading to high mortality rates worldwide, and to a large societal economic burden [1]. A number of pandemic influenza vaccines have received marketing authorization [2]. An increase in hemagglutination inhibition (HAI) antibody titer is commonly used to measure the response to the vaccine. NK cells are described as crucial innate immune cells in the fight against influenza infections [5]. Recent findings in NK cell biology provide further evidence on specific functional features of NK cells, which highlight a formerly underestimated role during infection. It was discovered that NK cells display adaptive immune features similar to T cells, including the generation of memory-like NK cells [10,11].
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