Differential gene expression in peripheral blood mononuclear cells from children immunized with inactivated influenza vaccine

ABSTRACT

The human immune response to inactivated influenza vaccine is dynamic and impacted by age and preexisting immunity. Our goal was to identify postvaccination transcriptomic changes in peripheral blood mononuclear cells from children. Blood samples were obtained before and at 3 or 7 days postvaccination with 2016–2017 quadrivalent inactivated influenza vaccine and RNA sequencing was performed. There were 1,466 differentially expressed genes (DEGs) for the Day 0–Day 3 group and 513 DEGs for the Day 0–Day 7 group. Thirty-three genes were common between the two groups. The majority of the transcriptomic changes at Day 3 represented innate inflammation and apoptosis pathways. Day 7 DEGs were characterized by activation of cellular processes, including the regulation of cytoskeleton, junctions, and metabolism, and increased expression of immunoglobulin genes. DEGs at Day 3 were compared between older and younger children revealing increased inflammatory gene expression in the older group. Vaccine history in the year prior to the study was characterized by robust DEGs at Day 3 with decreased phagosome and dendritic cell maturation in those who had been vaccinated in the previous year. PBMC responses to inactivated influenza vaccination in children differed significantly by the timing of sampling, patient age, and vaccine history. These data provide insight into the expected molecular pathways to be temporally altered by influenza vaccination in children.

KEYWORDS:

• Influenza
• RNA sequencing
• immunity
• pediatrics
• inflammation

Disclosure of potential conflict of interest

Drs. Zimmerman and Lin have research funding from Sanofi Pasteur, Inc. and Merck & Co, Inc. Drs. Zimmerman and Nowalk have research funding from Pfizer, Inc. and Merck & Co., Inc. Dr. Alcorn and Dr. Martin have research funding from MedImmune, LLC.

Author contributions

KSC, JMM and RKZ obtained funding. The study was designed by JFA, MPN, RKZ, KSC, KKM, and JMM. The study was conducted by MAO, WTH, JPN, and KKM. Data analyses were performed by RA, AC, CJL and URC. The manuscript was written by JFA, MPN, and JMM. All authors approved of the final manuscript.

Please note KSC - Kelly S. Cole, PhD is no longer at the Center for Vaccine Research, her current affiliation is: Director of Microbiology, Allegheny Health Network1307 Federal Street, Rm. 111, Pittsburgh, PA 15212 [email protected].

Abbreviations

ACIP	=	Advisory Committee on Immunization Practices
AAP	=	American Academy of Pediatrics
CDC	=	Centers for Disease Control and Prevention
CTSI	=	Clinical Translational Science Institute
DEGs	=	Differentially expressed transcripts
EMR	=	Electronic medical record
HI	=	Hemagglutinin inhibition
IIV	=	Inactivated influenza vaccine
LAIV	=	Live attenuated influenza vaccine
NCATS	=	National Center for Advancing Translational Sciences
NIH	=	National Institutes of Health
PBMC	=	Peripheral blood mononuclear cells
FDR	=	False Discovery Rate

Additional information

Funding

This work was supported by the Centers for Disease Control and Prevention (CDC), through cooperative agreements with the University of Pittsburgh [grant U01 IP000467 and IP001035] and by the National Institutes of Health (NIH) [grant UL1 TR001857] to the University of Pittsburgh. Also by the CTSI Translational Research Pilot Awards National Institutes of Health [UL1TR001857], from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of CDC, NCATS or NIH. Information on NCATS is available at http://www.ncats.nih.gov/.