tetano
Editor, Senior Moderator
JCI Insight
. 2025 Mar 4:e184128.
doi: 10.1172/jci.insight.184128. Online ahead of print. Boosting effect of high-dose influenza vaccination on innate immunity among elderly: a randomized-control trial
Olivia Bonduelle[SUP] 1 [/SUP], Tristan Delory[SUP] 2 [/SUP], Isabelle Franco Moscardini[SUP] 1 [/SUP], Marion Ghidi[SUP] 2 [/SUP], Selma Bennacer[SUP] 1 [/SUP], Michele Wokam[SUP] 1 [/SUP], Mathieu Lenormand[SUP] 2 [/SUP], Melissa Petrier[SUP] 2 [/SUP], Olivier Rogeaux[SUP] 3 [/SUP], Simon de Bernard[SUP] 4 [/SUP], Karine Alves[SUP] 4 [/SUP], Julien Nourikyan[SUP] 4 [/SUP], Bruno Lina[SUP] 5 [/SUP], Behazine Combadiere[SUP] 1 [/SUP], Cécile Janssen[SUP] 2 [/SUP]
Affiliations
Background: The high-dose quadrivalent influenza vaccine (QIV-HD) showed superior efficacy against laboratory-confirmed illness than the standard-dose quadrivalent influenza vaccine (QIV-SD) in randomized-controlled trials with elderly. However, specific underlying mechanism remains unclear.
Methods: This Phase-IV randomized control trial compared early innate responses induced by QIV-HD and QIV-SD in 59 subjects aged >65 years. Systemic innate cells and gene signatures at Day (D) 0 and D1, hemagglutinin inhibition antibody (HIA) titers at D0 and D21 post-vaccination were assessed.
Results: QIV-HD elicited robust humoral response with significantly higher antibody titers and seroconversion rates than QIV-SD. At D1 post-vaccination, QIV-HD recipients showed significant reduction in innate cells, including conventional dendritic cells and natural killer cells than QIV-SD, correlating with significantly increased HIA titers at D21. Blood transcriptomic analysis revealed greater amplitude of gene expression in QIV-HD arm, encompassing genes related to innate immune response, interferons, 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 Number: 2021-004573-32.
Keywords: Immunology; Influenza; Innate immunity; Vaccines.
. 2025 Mar 4:e184128.
doi: 10.1172/jci.insight.184128. Online ahead of print. Boosting effect of high-dose influenza vaccination on innate immunity among elderly: a randomized-control trial
Olivia Bonduelle[SUP] 1 [/SUP], Tristan Delory[SUP] 2 [/SUP], Isabelle Franco Moscardini[SUP] 1 [/SUP], Marion Ghidi[SUP] 2 [/SUP], Selma Bennacer[SUP] 1 [/SUP], Michele Wokam[SUP] 1 [/SUP], Mathieu Lenormand[SUP] 2 [/SUP], Melissa Petrier[SUP] 2 [/SUP], Olivier Rogeaux[SUP] 3 [/SUP], Simon de Bernard[SUP] 4 [/SUP], Karine Alves[SUP] 4 [/SUP], Julien Nourikyan[SUP] 4 [/SUP], Bruno Lina[SUP] 5 [/SUP], Behazine Combadiere[SUP] 1 [/SUP], Cécile Janssen[SUP] 2 [/SUP]
Affiliations
- PMID: 40036077
- DOI: 10.1172/jci.insight.184128
Background: The high-dose quadrivalent influenza vaccine (QIV-HD) showed superior efficacy against laboratory-confirmed illness than the standard-dose quadrivalent influenza vaccine (QIV-SD) in randomized-controlled trials with elderly. However, specific underlying mechanism remains unclear.
Methods: This Phase-IV randomized control trial compared early innate responses induced by QIV-HD and QIV-SD in 59 subjects aged >65 years. Systemic innate cells and gene signatures at Day (D) 0 and D1, hemagglutinin inhibition antibody (HIA) titers at D0 and D21 post-vaccination were assessed.
Results: QIV-HD elicited robust humoral response with significantly higher antibody titers and seroconversion rates than QIV-SD. At D1 post-vaccination, QIV-HD recipients showed significant reduction in innate cells, including conventional dendritic cells and natural killer cells than QIV-SD, correlating with significantly increased HIA titers at D21. Blood transcriptomic analysis revealed greater amplitude of gene expression in QIV-HD arm, encompassing genes related to innate immune response, interferons, 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 Number: 2021-004573-32.
Keywords: Immunology; Influenza; Innate immunity; Vaccines.