Memory-like innate response to booster vaccination with MF-59 adjuvanted influenza vaccine in children

• Type of Material: Article
• Authors: Dmitri Kazmin, Stanford University; Elizabeth A Clutterbuck, University of Oxford; Giorgio Napolitani, University of Oxford; Amanda L Wilkins, University of Oxford; Andrea Tarlton, University of Oxford; Amber J Thompson, University of Oxford; Emmanuele Montomoli, University of Siena; Guilia Lapini, VisMederi Srl, Via Fiorentina, Siena; Smiti Bihari, University of Oxford; Rachel White, University of Oxford; Claire Jones, University of Oxford; Matthew D Snape, University of Oxford; Ushma Galal, University of Oxford; Ly-Mee Yu, University of Oxford; Rino Rappuoli, Fondazione Biotecnopolo, Siena; Giuseppe Del Giudice, GlaxoSmithKline, Siena; Andrew J Pollard, University of Oxford; Bali Pulendran, Emory University
• Language: English
• Date: 2023-07-14
• Publisher: Nature Research (part of Springer Nature)
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2023
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41541-023-00702-1
• Title of Journal or Parent Work: npj Vaccines
• Volume: 8
• Grant/Funding Information: European Commission program Advanced Immunization Technologies (ADITEC) and the NIHR Oxford Biomedical Research Centre.
• Keywords: Protein vaccines; Adjuvants
• Research Categories: Biology, Molecular; Health Sciences, Immunology; Health Sciences, Pathology

Abstract

The pediatric population receives the majority of vaccines globally, yet there is a paucity of studies on the transcriptional response induced by immunization in this special population. In this study, we performed a systems-level analysis of immune responses to the trivalent inactivated influenza vaccine adjuvanted with MF-59 in children (15–24 months old) and in young, healthy adults. We analyzed transcriptional responses elicited by vaccination in peripheral blood, as well as cellular and antibody responses following primary and booster vaccinations. Our analysis revealed that primary vaccination induced a persistent transcriptional signature of innate immunity; booster vaccination induced a transcriptional signature of an enhanced memory-like innate response, which was consistent with enhanced activation of myeloid cells assessed by flow cytometry. Furthermore, we identified a transcriptional signature of type 1 interferon response post-booster vaccination and at baseline that was correlated with the local reactogenicity to vaccination and defined an early signature that correlated with the hemagglutinin antibody titers. These results highlight an adaptive behavior of the innate immune system in evoking a memory-like response to secondary vaccination and define molecular correlates of reactogenicity and immunogenicity in infants.