Proteomic Signatures of the Serological Response to Influenza Vaccination in a Large Human Cohort Study

The serological response to the influenza virus vaccine is highly heterogeneous for reasons that are not entirely clear. While the impact of demographic factors such as age, body mass index (BMI), sex, prior vaccination and titer levels are known to impact seroconversion, they only explain a fractio...

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Main Authors: Shaohuan Wu, Smruti Pushalkar, Shuvadeep Maity, Matthew Pressler, Justin Rendleman, Burcu Vitrinel, Michael Carlock, Ted Ross, Hyungwon Choi, Christine Vogel
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/14/11/2479
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author Shaohuan Wu
Smruti Pushalkar
Shuvadeep Maity
Matthew Pressler
Justin Rendleman
Burcu Vitrinel
Michael Carlock
Ted Ross
Hyungwon Choi
Christine Vogel
author_facet Shaohuan Wu
Smruti Pushalkar
Shuvadeep Maity
Matthew Pressler
Justin Rendleman
Burcu Vitrinel
Michael Carlock
Ted Ross
Hyungwon Choi
Christine Vogel
author_sort Shaohuan Wu
collection DOAJ
description The serological response to the influenza virus vaccine is highly heterogeneous for reasons that are not entirely clear. While the impact of demographic factors such as age, body mass index (BMI), sex, prior vaccination and titer levels are known to impact seroconversion, they only explain a fraction of the response. To identify signatures of the vaccine response, we analyzed 273 protein levels from 138 serum samples of influenza vaccine recipients (2019–2020 season). We found that levels of proteins functioning in cholesterol transport were positively associated with seroconversion, likely linking to the known impact of BMI. When adjusting seroconversion for the demographic factors, we identified additional, unexpected signatures: proteins regulating actin cytoskeleton dynamics were significantly elevated in participants with high adjusted seroconversion. Viral strain specific analysis showed that this trend was largely driven by the H3N2 strain. Further, we identified complex associations between adjusted seroconversion and other factors: levels of proteins of the complement system associated positively with adjusted seroconversion in younger participants, while they were associated negatively in the older population. We observed the opposite trends for proteins of high density lipoprotein remodeling, transcription, and hemostasis. In sum, careful integrative modeling can extract new signatures of seroconversion from highly variable data that suggest links between the humoral response as well as immune cell communication and migration.
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spelling doaj.art-55da944997a740ea8db8fa17f04a8fcf2023-11-24T07:17:53ZengMDPI AGViruses1999-49152022-11-011411247910.3390/v14112479Proteomic Signatures of the Serological Response to Influenza Vaccination in a Large Human Cohort StudyShaohuan Wu0Smruti Pushalkar1Shuvadeep Maity2Matthew Pressler3Justin Rendleman4Burcu Vitrinel5Michael Carlock6Ted Ross7Hyungwon Choi8Christine Vogel9Center for Genomics and Systems Biology, New York University, New York, NY 10003, USACenter for Genomics and Systems Biology, New York University, New York, NY 10003, USACenter for Genomics and Systems Biology, New York University, New York, NY 10003, USACenter for Genomics and Systems Biology, New York University, New York, NY 10003, USACenter for Genomics and Systems Biology, New York University, New York, NY 10003, USACenter for Genomics and Systems Biology, New York University, New York, NY 10003, USADepartment of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USADepartment of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USADepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, SingaporeCenter for Genomics and Systems Biology, New York University, New York, NY 10003, USAThe serological response to the influenza virus vaccine is highly heterogeneous for reasons that are not entirely clear. While the impact of demographic factors such as age, body mass index (BMI), sex, prior vaccination and titer levels are known to impact seroconversion, they only explain a fraction of the response. To identify signatures of the vaccine response, we analyzed 273 protein levels from 138 serum samples of influenza vaccine recipients (2019–2020 season). We found that levels of proteins functioning in cholesterol transport were positively associated with seroconversion, likely linking to the known impact of BMI. When adjusting seroconversion for the demographic factors, we identified additional, unexpected signatures: proteins regulating actin cytoskeleton dynamics were significantly elevated in participants with high adjusted seroconversion. Viral strain specific analysis showed that this trend was largely driven by the H3N2 strain. Further, we identified complex associations between adjusted seroconversion and other factors: levels of proteins of the complement system associated positively with adjusted seroconversion in younger participants, while they were associated negatively in the older population. We observed the opposite trends for proteins of high density lipoprotein remodeling, transcription, and hemostasis. In sum, careful integrative modeling can extract new signatures of seroconversion from highly variable data that suggest links between the humoral response as well as immune cell communication and migration.https://www.mdpi.com/1999-4915/14/11/2479influenza vaccinationserological responseserum proteomicscohort analysesseroconversion
spellingShingle Shaohuan Wu
Smruti Pushalkar
Shuvadeep Maity
Matthew Pressler
Justin Rendleman
Burcu Vitrinel
Michael Carlock
Ted Ross
Hyungwon Choi
Christine Vogel
Proteomic Signatures of the Serological Response to Influenza Vaccination in a Large Human Cohort Study
Viruses
influenza vaccination
serological response
serum proteomics
cohort analyses
seroconversion
title Proteomic Signatures of the Serological Response to Influenza Vaccination in a Large Human Cohort Study
title_full Proteomic Signatures of the Serological Response to Influenza Vaccination in a Large Human Cohort Study
title_fullStr Proteomic Signatures of the Serological Response to Influenza Vaccination in a Large Human Cohort Study
title_full_unstemmed Proteomic Signatures of the Serological Response to Influenza Vaccination in a Large Human Cohort Study
title_short Proteomic Signatures of the Serological Response to Influenza Vaccination in a Large Human Cohort Study
title_sort proteomic signatures of the serological response to influenza vaccination in a large human cohort study
topic influenza vaccination
serological response
serum proteomics
cohort analyses
seroconversion
url https://www.mdpi.com/1999-4915/14/11/2479
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