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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 1 , Srabanti Rakshit 1 , Vasista Adiga 1 , Asma Ahmed 1 , Nirutha Chetan Kumar 1 , Maria Macrina 1 , Himanshu Tripathi 1 , Francesca Vanni 2 , Emanuele Montomoli 2 , Sweety Samal 3 , Sneha Raj 3 , Preeti Vishwakarma 3 , George D Souza 4 , Shruthi Sasidharan 5 , Mary Dias 5 , Timothy Tree 6 , Annapurna Vyakarnam 7 8
Affiliations
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 FluarixTM Tetra (GlaxoSmithKlein) 2022/2023 NH Vaccine in 2022. Significant induction of hemagglutinin inhibition-specific antibodies and polyfunctional central memory CD4+ T-cells (TCM) were observed 1-week post-vaccination with variable induction of CD8+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. FluarixTM 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+IL1β+HLA-DR+CD14+CD16- 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.
. 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 1 , Srabanti Rakshit 1 , Vasista Adiga 1 , Asma Ahmed 1 , Nirutha Chetan Kumar 1 , Maria Macrina 1 , Himanshu Tripathi 1 , Francesca Vanni 2 , Emanuele Montomoli 2 , Sweety Samal 3 , Sneha Raj 3 , Preeti Vishwakarma 3 , George D Souza 4 , Shruthi Sasidharan 5 , Mary Dias 5 , Timothy Tree 6 , Annapurna Vyakarnam 7 8
Affiliations
- PMID: 41453905
- DOI: 10.1038/s41541-025-01331-6
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 FluarixTM Tetra (GlaxoSmithKlein) 2022/2023 NH Vaccine in 2022. Significant induction of hemagglutinin inhibition-specific antibodies and polyfunctional central memory CD4+ T-cells (TCM) were observed 1-week post-vaccination with variable induction of CD8+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. FluarixTM 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+IL1β+HLA-DR+CD14+CD16- 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.