Abstract
BackgroundPrevious 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.MethodsCellular flu-specific immune responses were assessed by whole-blood antigen stimulation assay, and humoral responses by a single radial hemolysis test.ResultsPrevious 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.ConclusionsStrong 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.
Highlights
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
We evaluated the impact of previous flu vaccinations on IFN-γ production and A/H1N1/California/7/2009specific Ab levels measured by Single radial haemolysis (SRH) at study entry (Table 1)
This study showed that pdm flu vaccination (A/California/ 7/2009) induced increased levels of A/H1N1/California/7/ 2009-specific Abs, and strong immune cellular responses directed against flu A antigens from H1N1, H3N2 and H5N1 strains, flu B strains, and the flu M1 matrix antigen
Summary
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. It is estimated that in the United States pdmH1N1 caused higher rates of hospitalizations and deaths in children and adults 18–64 years of age than the flu of the previous season, but lower rates of clinical events in adults over 65 years of age [4]. This finding supports the notion that previous exposures to H1N1 in older individuals provides higher cross-protective immune responses than in younger individuals [5]. In the autumn of 2009, pdmH1N1 vaccines (pdm vaccines) were available across the globe, it was estimated that pdmH1N1 vaccination prevented 4,000–10,000 hospitalizations and 200–500 deaths in the US [6]
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