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

Magalhaes I, Eriksson M, Linde C, Muhammad R, Rane L, Ambati A, Axelsson-Robertson R, Khalaj B, Alvarez-Corrales N, Lapini G, Montomoli E, Linde A, Pedersen NL, Maeurer M - BMC Infect. Dis. (2014)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for allogeneic stem cell transplantation, Karolinska University Hospital, Stockholm, Sweden. markus.maeurer@ki.se.

ABSTRACT

Background: 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.

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

Results: 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.

Conclusions: 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.

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Related in: MedlinePlus

Overview of the ILI study participants. 1,971 study participants entered the study in the winter of 2009 (time point A); 67 samples were collected from study participants and household members during home visits triggered by an H1N1+ or coronavirus + PCR (detected in nasal swabs sent at time point B); 918 study participants returned for the follow-up sampling in the spring of 2010 (time point C).
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Figure 1: Overview of the ILI study participants. 1,971 study participants entered the study in the winter of 2009 (time point A); 67 samples were collected from study participants and household members during home visits triggered by an H1N1+ or coronavirus + PCR (detected in nasal swabs sent at time point B); 918 study participants returned for the follow-up sampling in the spring of 2010 (time point C).

Mentions: After quality control (i.e. exclusion of samples without identification), the analysis group consisted of 1,971 participants: 1,807 adults aged between 18 and 65 years (median age 36, 53% women), 155 adults over 65 (median age 71 years, 65% women), and 9 children with a median age of 8 years. The baseline step (autumn/winter 2009) is designated time point ‘A’, and the event step (autumn/winter 2009) is designated time point ‘B’. Altogether, 466 study participants mailed a swab for viral pathogen analysis and 618 participants filed a self-report (flu event questionnaire). For 41 study participants, a positive H1N1 or coronavirus PCR (for controls) triggered a home visit from a nurse to study the immune response at an early time point. The final step (spring 2010) is designated time point ‘C’, where 918 study participants (46.6% of the initial number of participants) again provided a blood sample (see overview of the study in Figure 1). This allowed us to study the humoral and cellular immune responses directed against flu—and also against control antigens—in an unbiased way.


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

Magalhaes I, Eriksson M, Linde C, Muhammad R, Rane L, Ambati A, Axelsson-Robertson R, Khalaj B, Alvarez-Corrales N, Lapini G, Montomoli E, Linde A, Pedersen NL, Maeurer M - BMC Infect. Dis. (2014)

Overview of the ILI study participants. 1,971 study participants entered the study in the winter of 2009 (time point A); 67 samples were collected from study participants and household members during home visits triggered by an H1N1+ or coronavirus + PCR (detected in nasal swabs sent at time point B); 918 study participants returned for the follow-up sampling in the spring of 2010 (time point C).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4067073&req=5

Figure 1: Overview of the ILI study participants. 1,971 study participants entered the study in the winter of 2009 (time point A); 67 samples were collected from study participants and household members during home visits triggered by an H1N1+ or coronavirus + PCR (detected in nasal swabs sent at time point B); 918 study participants returned for the follow-up sampling in the spring of 2010 (time point C).
Mentions: After quality control (i.e. exclusion of samples without identification), the analysis group consisted of 1,971 participants: 1,807 adults aged between 18 and 65 years (median age 36, 53% women), 155 adults over 65 (median age 71 years, 65% women), and 9 children with a median age of 8 years. The baseline step (autumn/winter 2009) is designated time point ‘A’, and the event step (autumn/winter 2009) is designated time point ‘B’. Altogether, 466 study participants mailed a swab for viral pathogen analysis and 618 participants filed a self-report (flu event questionnaire). For 41 study participants, a positive H1N1 or coronavirus PCR (for controls) triggered a home visit from a nurse to study the immune response at an early time point. The final step (spring 2010) is designated time point ‘C’, where 918 study participants (46.6% of the initial number of participants) again provided a blood sample (see overview of the study in Figure 1). This allowed us to study the humoral and cellular immune responses directed against flu—and also against control antigens—in an unbiased way.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for allogeneic stem cell transplantation, Karolinska University Hospital, Stockholm, Sweden. markus.maeurer@ki.se.

ABSTRACT

Background: 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.

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

Results: 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.

Conclusions: 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.

Show MeSH
Related in: MedlinePlus