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

Dmitri Kazmin; Elizabeth A Clutterbuck; Giorgio Napolitani; Amanda L Wilkins; Andrea Tarlton; Amber J Thompson; Emmanuele Montomoli; Guilia Lapini; Smiti Bihari; Rachel White; Claire Jones; Matthew D Snape; Ushma Galal; Ly-Mee Yu; Rino Rappuoli; Giuseppe Del Giudice; Andrew J Pollard; Bali Pulendran

doi:10.1038/s41541-023-00702-1

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

NPJ Vaccines. 2023 Jul 13;8(1):100. doi: 10.1038/s41541-023-00702-1.

Authors

Dmitri Kazmin^#¹, Elizabeth A Clutterbuck^#², Giorgio Napolitani^#³, Amanda L Wilkins^#^{2

4}, Andrea Tarlton³, Amber J Thompson², Emmanuele Montomoli^{5

6}, Guilia Lapini⁵, Smiti Bihari², Rachel White², Claire Jones², Matthew D Snape², Ushma Galal⁷, Ly-Mee Yu⁷, Rino Rappuoli^{8

9}, Giuseppe Del Giudice⁸, Andrew J Pollard¹⁰, Bali Pulendran^{11

12

13

14}

Affiliations

¹ Institute for Immunology, Transplantation and Infection, Stanford University, Stanford, CA, USA. dkazmin@stanford.edu.
² Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
³ Medical Research Council (MRC), Human Immunology Unit, University of Oxford, Oxford, UK.
⁴ The Royal Children's Hospital Melbourne, Parkville, VIC, Australia.
⁵ VisMederi Srl, Via Fiorentina, Siena, Italy.
⁶ Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
⁷ Nuffield Department of Primary Care Health Sciences, Clinical Trials Unit, University of Oxford, Oxford, UK.
⁸ GlaxoSmithKline, Siena, Italy.
⁹ Fondazione Biotecnopolo, Siena, Italy.
¹⁰ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, UK. andrew.pollard@paediatrics.ox.ac.uk.
¹¹ Institute for Immunology, Transplantation and Infection, Stanford University, Stanford, CA, USA. bpulend@stanford.edu.
¹² Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA. bpulend@stanford.edu.
¹³ Department of Pathology, and Microbiology & Immunology, Stanford University, Stanford, CA, USA. bpulend@stanford.edu.
¹⁴ Emory Vaccine Center, Emory University, Atlanta, GA, USA. bpulend@stanford.edu.

^# Contributed equally.

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.

Abstract

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