Proteomics show antigen presentation processes in human immune cells after AS03-H5N1 vaccination.
AUTHORS
- PMID: 28508465 [PubMed].
ABSTRACT
Adjuvants enhance immunity elicited by vaccines through mechanisms that are poorly understood. Using a systems biology approach, we investigated temporal protein expression changes in five primary human immune cell populations: neutrophils, monocytes, natural killer (NK) cells, T-cells, and B-cells after administration of either an Adjuvant System 03 (AS03)-adjuvanted or unadjuvanted split-virus H5N1 influenza vaccine. Monocytes demonstrated the strongest differential signal between vaccine groups. On day 3 post-vaccination, several antigen presentation-related pathways, including MHC class I-mediated antigen processing and presentation, were enriched in monocytes and neutrophils and expression of HLA Class I proteins was increased in the AS03 group. We identified several protein families whose proteomic responses predicted seroprotective antibody responses (>1:40 Hemagglutination inhibition titer), including inflammation and oxidative stress proteins at day 1 as well as immunoproteasome subunit (PSME1 and PSME2) and HLA Class I proteins at day 3 in monocytes. While comparison between temporal proteomic and transcriptomic results showed little overlap overall, enrichment of the MHC Class I antigen processing and presentation pathway in monocytes and neutrophils was confirmed by both approaches. This article is protected by copyright. All rights reserved.
Adjuvants enhance immunity elicited by vaccines through mechanisms that are poorly understood. Using a systems biology approach, we investigated temporal protein expression changes in five primary human immune cell populations: neutrophils, monocytes, natural killer (NK) cells, T-cells, and B-cells after administration of either an Adjuvant System 03 (AS03)-adjuvanted or unadjuvanted split-virus H5N1 influenza vaccine. Monocytes demonstrated the strongest differential signal between vaccine groups. On day 3 post-vaccination, several antigen presentation-related pathways, including MHC class I-mediated antigen processing and presentation, were enriched in monocytes and neutrophils and expression of HLA Class I proteins was increased in the AS03 group. We identified several protein families whose proteomic responses predicted seroprotective antibody responses (>1:40 Hemagglutination inhibition titer), including inflammation and oxidative stress proteins at day 1 as well as immunoproteasome subunit (PSME1 and PSME2) and HLA Class I proteins at day 3 in monocytes. While comparison between temporal proteomic and transcriptomic results showed little overlap overall, enrichment of the MHC Class I antigen processing and presentation pathway in monocytes and neutrophils was confirmed by both approaches. This article is protected by copyright. All rights reserved.
Tags: Alumni Publications 2017