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NPJ Vaccines . Influenza vaccination post-COVID-19 expands vaccine-specific effector CD4 T-cells and Tregs under positive influence of host trained

tetano

Editor, Senior Moderator
NPJ Vaccines


. 2025 Dec 26.
doi: 10.1038/s41541-025-01331-6. Online ahead of print. Influenza vaccination post-COVID-19 expands vaccine-specific effector CD4 T-cells and Tregs under positive influence of host trained innate immunity

Hima Bindhu[SUP] 1 [/SUP], Srabanti Rakshit[SUP] 1 [/SUP], Vasista Adiga[SUP] 1 [/SUP], Asma Ahmed[SUP] 1 [/SUP], Nirutha Chetan Kumar[SUP] 1 [/SUP], Maria Macrina[SUP] 1 [/SUP], Himanshu Tripathi[SUP] 1 [/SUP], Francesca Vanni[SUP] 2 [/SUP], Emanuele Montomoli[SUP] 2 [/SUP], Sweety Samal[SUP] 3 [/SUP], Sneha Raj[SUP] 3 [/SUP], Preeti Vishwakarma[SUP] 3 [/SUP], George D Souza[SUP] 4 [/SUP], Shruthi Sasidharan[SUP] 5 [/SUP], Mary Dias[SUP] 5 [/SUP], Timothy Tree[SUP] 6 [/SUP], Annapurna Vyakarnam[SUP] 7 8 [/SUP]



Affiliations
Abstract

SARS-CoV-2 immunity and innate immune training may influence influenza vaccine immunogenicity. We investigated this in India. Adult volunteers with hybrid SARS-CoV-2 immunity were administered Fluarix[SUP]TM[/SUP] Tetra (GlaxoSmithKlein) 2022/2023 NH Vaccine in 2022. Significant induction of hemagglutinin inhibition-specific antibodies and polyfunctional central memory CD4[SUP]+[/SUP] T-cells (TCM) were observed 1-week post-vaccination with variable induction of CD8[SUP]+[/SUP]T-cell and innate effectors. Vaccination also expanded Flu-specific regulatory T-cells (Treg), which negatively correlated with CD4 responses, highlighting vaccine immunogenicity may be subject to Treg dampening. Fluarix[SUP]TM[/SUP] did not boost SARS-CoV-2 immunity. However, SARS-CoV-2-specific T-cell responses correlated positively with vaccine-induced T-cell responses. We evaluated trained immunity post-COVID-19 as a potential regulatory mechanism linking SARS-CoV-2 and heterologous vaccine immunogenicity. We observed, elevated frequencies of basal bacterial Lipopolysaccharide (LPS)-induced IL-6[SUP]+[/SUP]IL1β[SUP]+[/SUP]HLA-DR[SUP]+[/SUP]CD14[SUP]+[/SUP]CD16[SUP]-[/SUP] frequencies post-COVID-19 correlated positively with vaccine-induced Fluarix-specific CD4 T-cell frequencies. Our study highlights a potential positive role for COVID-19-driven immune imprinting on heterologous vaccine immunogenicity in a post-COVID-19 era.


 
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