Boosting effect of high-dose influenza vaccination on innate immunity among elderly
Olivia Bonduelle, Tristan Delory, Isabelle Franco-Moscardini, Marion Ghidi, Selma Bennacer, Michele Wokam, Mathieu Lenormand, Melissa Petrier, Olivier Rogeaux, Simon de Bernard, Karine Alves, Julien Nourikyan, Bruno Lina, INFLUOMICS Study group, Behazine Combadiere, Cécile Janssen
Olivia Bonduelle, Tristan Delory, Isabelle Franco-Moscardini, Marion Ghidi, Selma Bennacer, Michele Wokam, Mathieu Lenormand, Melissa Petrier, Olivier Rogeaux, Simon de Bernard, Karine Alves, Julien Nourikyan, Bruno Lina, INFLUOMICS Study group, Behazine Combadiere, Cécile Janssen
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Clinical Research and Public Health Immunology Vaccines

Boosting effect of high-dose influenza vaccination on innate immunity among elderly

Abstract

BACKGROUND The high-dose quadrivalent influenza vaccine (QIV-HD) showed superior efficacy against laboratory-confirmed illness compared with the standard-dose quadrivalent influenza vaccine (QIV-SD) in randomized controlled trials with the elderly. However, specific underlying mechanism remains unclear.METHODS This phase IV randomized controlled trial compared early innate responses induced by QIV-HD and QIV-SD in 59 individuals aged > 65 years. Systemic innate cells and gene signatures at day 0 (D0) and D1 as well as hemagglutinin inhibition antibody (HIA) titers at D0 and D21 after vaccination were assessed.RESULTS QIV-HD elicited robust humoral response with significantly higher antibody titers and seroconversion rates than QIV-SD. At D1 after vaccination, QIV-HD recipients showed significant reduction in innate cells, including conventional DCs and NK cells, compared with QIV-SD, correlating with significantly increased HIA titers at D21. Blood transcriptomic analysis revealed greater amplitude of gene expression in the QIV-HD arm, encompassing genes related to innate immune response, IFNs, and antigen processing and presentation, and correlated with humoral responses. Interestingly, comparative analysis with a literature dataset from young adults vaccinated with influenza standard-dose vaccine highlighted strong similarities in gene expression patterns and biological pathways with the elderly vaccinated with QIV-HD.CONCLUSION QIV-HD induces higher HIA titers than QIV-SD, a youthful boost of the innate gene expression significantly associated with high HIA titers.TRIAL REGISTRATION EudraCT no. 2021-004573-32.

Authors

Olivia Bonduelle, Tristan Delory, Isabelle Franco-Moscardini, Marion Ghidi, Selma Bennacer, Michele Wokam, Mathieu Lenormand, Melissa Petrier, Olivier Rogeaux, Simon de Bernard, Karine Alves, Julien Nourikyan, Bruno Lina, INFLUOMICS Study group, Behazine Combadiere, Cécile Janssen

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Figure 5

Significant up- and downregulated gene associated with early innate response modules in elderly individuals vaccinated with QIV-SD and QIV-HD compared with young adults vaccinated with TIV-SD.

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Significant up- and downregulated gene associated with early innate resp...
(A) The tmod enrichment analysis for QIV-SD, QIV-HD and young adults vaccinated with TIV-SD. From the list of genes provided by the limma R package, genes were ranked by their P values, and the enriched blood transcription modules were obtained by the CERNO test. The effect size is proportional to the size of the pie, while the adjusted P value is proportional to color intensity. Within each pie, the proportion of significantly upregulated and downregulated genes is shown in red and blue, respectively. The gray portion of the pie represents genes that are not significantly differentially regulated. (B) Heatmap of the log2 FC of the biomarkers of immune response that belong to the IFN signaling pathway, comparing the QIV-SD and QIV-HD arms with the meta-analysis of studies with young adults vaccinated with TIV-SD. The combining approach from the MetavolcanoR package was used to summarize the FC of the studies based on the mean of the values, while the P value was combined using the Fisher method.