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Difference in immune response in vaccinated and unvaccinated Swedish individuals after the 2009 influenza pandemic

Isabelle Magalhaes12, Mikael Eriksson3, Charlotte Linde4, Rashid Muhammad4, Lalit Rane4, Aditya Ambati12, Rebecca Axelsson-Robertson12, Bahareh Khalaj4, Nancy Alvarez-Corrales4, Giulia Lapini5, Emanuele Montomoli5, Annika Linde6, Nancy L Pedersen3 and Markus Maeurer1247*

Author Affiliations

1 Center for allogeneic stem cell transplantation, Karolinska University Hospital, Stockholm, Sweden

2 Department of Laboratory Medicine, Division of Therapeutic Immunology, Karolinska Institute, Stockholm, Sweden

3 Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden

4 Microbiology, Tumor and Cell Biology, MTB, Karolinska Institutet, Stockholm, Sweden

5 Department of Physiopathology, Molecular Epidemiology Research Division, Experimental Medicine and Public Health, University of Siena, Siena, Italy

6 Swedish Institute for Communicable Disease Control Stockholm, Smittskyddsinstitutet, Solna, Sweden

7 Therapeutic Immunology, F79, LabMed, Hälsovägen, Karolinska University Hospital Huddinge, SE-14186 Huddinge, Sweden

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BMC Infectious Diseases 2014, 14:319  doi:10.1186/1471-2334-14-319

Published: 11 June 2014



Previous exposures to flu and subsequent immune responses may impact on 2009/2010 pandemic flu vaccine responses and clinical symptoms upon infection with the 2009 pandemic H1N1 influenza strain. Qualitative and quantitative differences in humoral and cellular immune responses associated with the flu vaccination in 2009/2010 (pandemic H1N1 vaccine) and natural infection have not yet been described in detail. We designed a longitudinal study to examine influenza- (flu-) specific immune responses and the association between pre-existing flu responses, symptoms of influenza-like illness (ILI), impact of pandemic flu infection, and pandemic flu vaccination in a cohort of 2,040 individuals in Sweden in 2009–2010.


Cellular flu-specific immune responses were assessed by whole-blood antigen stimulation assay, and humoral responses by a single radial hemolysis test.


Previous seasonal flu vaccination was associated with significantly lower flu-specific IFN-γ responses (using a whole-blood assay) at study entry. Pandemic flu vaccination induced long-lived T-cell responses (measured by IFN-γ production) to influenza A strains, influenza B strains, and the matrix (M1) antigen. In contrast, individuals with pandemic flu infection (PCR positive) exhibited increased flu-specific T-cell responses shortly after onset of ILI symptoms but the immune response decreased after the flu season (spring 2010). We identified non-pandemic-flu vaccinated participants without ILI symptoms who showed an IFN-γ production profile similar to pandemic-flu infected participants, suggesting exposure without experiencing clinical symptoms.


Strong and long-lived flu-M1 specific immune responses, defined by IFN-γ production, in individuals after vaccination suggest that M1-responses may contribute to protective cellular immune responses. Silent flu infections appeared to be frequent in 2009/2010. The pandemic flu vaccine induced qualitatively and quantitatively different humoral and cellular immune responses as compared to infection with the 2009 H1N1 pandemic H1N1 influenza strain.

T-cells; H1N1; Immune protection; Flu antigens; Vaccine take; Epidemiology; Influenza; Pandemic