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Superior in vitro stimulation of human CD8+ T-cells by whole virus versus split virus influenza vaccines.

Halbroth BR, Heil A, Distler E, Dass M, Wagner EM, Plachter B, Probst HC, Strand D, Hartwig UF, Karner A, Aichinger G, Kistner O, Landfester K, Herr W - PLoS ONE (2014)

Bottom Line: Our study showed that influenza whole virus vaccines of major seasonal A and B strains activated DC more efficiently than those of pandemic swine-origin H1N1 and pandemic-like avian H5N1 strains.In contrast, influenza split virus vaccines had a low ability to activate DC, regardless which strain was investigated.We conclude that vaccines against seasonal and pandemic (-like) influenza strains that aim to stimulate cross-reacting CD8+ T cells should include whole virus rather than split virus formulations.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine III - University Medical Center of Johannes Gutenberg-University, Mainz, Germany.

ABSTRACT
Pandemic and seasonal influenza viruses cause considerable morbidity and mortality in the general human population. Protection from severe disease may result from vaccines that activate antigen-presenting DC for effective stimulation of influenza-specific memory T cells. Special attention is paid to vaccine-induced CD8+ T-cell responses, because they are mainly directed against conserved internal influenza proteins thereby presumably mediating cross-protection against circulating seasonal as well as emerging pandemic virus strains. Our study showed that influenza whole virus vaccines of major seasonal A and B strains activated DC more efficiently than those of pandemic swine-origin H1N1 and pandemic-like avian H5N1 strains. In contrast, influenza split virus vaccines had a low ability to activate DC, regardless which strain was investigated. We also observed that whole virus vaccines stimulated virus-specific CD8+ memory T cells much stronger compared to split virus counterparts, whereas both vaccine formats activated CD4+ Th cell responses similarly. Moreover, our data showed that whole virus vaccine material is delivered into the cytosolic pathway of DC for effective activation of virus-specific CD8+ T cells. We conclude that vaccines against seasonal and pandemic (-like) influenza strains that aim to stimulate cross-reacting CD8+ T cells should include whole virus rather than split virus formulations.

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Related in: MedlinePlus

Vaccine-induced DC maturation in healthy donor HD15.Immature DC of donor HD15 were incubated for 48(-like) and seasonal influenza virus vaccines at 10 µg/mL (referring to HA content) and were subsequently analyzed by flow cytometry for expression of maturation markers on viable 7AAD-negative cells (grey histograms). Split virus formulations were unavailable from pandemic (-like) strains A/H1N1-California and A/H5N1-Indonesia. Unfilled histograms represent IgG isotype control stainings. MFI values were added to each histogram. For abbreviations of virus strains see Table 1. s, split virus; w, whole virus; w/o, without.
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pone-0103392-g001: Vaccine-induced DC maturation in healthy donor HD15.Immature DC of donor HD15 were incubated for 48(-like) and seasonal influenza virus vaccines at 10 µg/mL (referring to HA content) and were subsequently analyzed by flow cytometry for expression of maturation markers on viable 7AAD-negative cells (grey histograms). Split virus formulations were unavailable from pandemic (-like) strains A/H1N1-California and A/H5N1-Indonesia. Unfilled histograms represent IgG isotype control stainings. MFI values were added to each histogram. For abbreviations of virus strains see Table 1. s, split virus; w, whole virus; w/o, without.

Mentions: Whole virus vaccines were analyzed for the ability to induce maturation in monocyte-derived immature DC of healthy individuals. Vaccines were available from seasonal strains A/H1N1-Brisbane, A/H3N2-Uruguay, and B/Brisbane, as well as from recent pandemic-like avian and pandemic swine-origin strains A/H5N1-Indonesia, A/H5N1-Vietnam, and A/H1N1-California, respectively (Table 1). Flow cytometry data on DC showed that incubation with seasonal whole virus vaccines strongly increased the expression of CD80, CD86, HLA-A/B/C, HLA-DR, CD40, CD83, consistent with a phenotype of mature DC (Fig. 1, Fig. 2A). This up-regulation was absent or observed at much lower level if pandemic (-like) whole virus vaccines were added to DC.


Superior in vitro stimulation of human CD8+ T-cells by whole virus versus split virus influenza vaccines.

Halbroth BR, Heil A, Distler E, Dass M, Wagner EM, Plachter B, Probst HC, Strand D, Hartwig UF, Karner A, Aichinger G, Kistner O, Landfester K, Herr W - PLoS ONE (2014)

Vaccine-induced DC maturation in healthy donor HD15.Immature DC of donor HD15 were incubated for 48(-like) and seasonal influenza virus vaccines at 10 µg/mL (referring to HA content) and were subsequently analyzed by flow cytometry for expression of maturation markers on viable 7AAD-negative cells (grey histograms). Split virus formulations were unavailable from pandemic (-like) strains A/H1N1-California and A/H5N1-Indonesia. Unfilled histograms represent IgG isotype control stainings. MFI values were added to each histogram. For abbreviations of virus strains see Table 1. s, split virus; w, whole virus; w/o, without.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4114834&req=5

pone-0103392-g001: Vaccine-induced DC maturation in healthy donor HD15.Immature DC of donor HD15 were incubated for 48(-like) and seasonal influenza virus vaccines at 10 µg/mL (referring to HA content) and were subsequently analyzed by flow cytometry for expression of maturation markers on viable 7AAD-negative cells (grey histograms). Split virus formulations were unavailable from pandemic (-like) strains A/H1N1-California and A/H5N1-Indonesia. Unfilled histograms represent IgG isotype control stainings. MFI values were added to each histogram. For abbreviations of virus strains see Table 1. s, split virus; w, whole virus; w/o, without.
Mentions: Whole virus vaccines were analyzed for the ability to induce maturation in monocyte-derived immature DC of healthy individuals. Vaccines were available from seasonal strains A/H1N1-Brisbane, A/H3N2-Uruguay, and B/Brisbane, as well as from recent pandemic-like avian and pandemic swine-origin strains A/H5N1-Indonesia, A/H5N1-Vietnam, and A/H1N1-California, respectively (Table 1). Flow cytometry data on DC showed that incubation with seasonal whole virus vaccines strongly increased the expression of CD80, CD86, HLA-A/B/C, HLA-DR, CD40, CD83, consistent with a phenotype of mature DC (Fig. 1, Fig. 2A). This up-regulation was absent or observed at much lower level if pandemic (-like) whole virus vaccines were added to DC.

Bottom Line: Our study showed that influenza whole virus vaccines of major seasonal A and B strains activated DC more efficiently than those of pandemic swine-origin H1N1 and pandemic-like avian H5N1 strains.In contrast, influenza split virus vaccines had a low ability to activate DC, regardless which strain was investigated.We conclude that vaccines against seasonal and pandemic (-like) influenza strains that aim to stimulate cross-reacting CD8+ T cells should include whole virus rather than split virus formulations.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine III - University Medical Center of Johannes Gutenberg-University, Mainz, Germany.

ABSTRACT
Pandemic and seasonal influenza viruses cause considerable morbidity and mortality in the general human population. Protection from severe disease may result from vaccines that activate antigen-presenting DC for effective stimulation of influenza-specific memory T cells. Special attention is paid to vaccine-induced CD8+ T-cell responses, because they are mainly directed against conserved internal influenza proteins thereby presumably mediating cross-protection against circulating seasonal as well as emerging pandemic virus strains. Our study showed that influenza whole virus vaccines of major seasonal A and B strains activated DC more efficiently than those of pandemic swine-origin H1N1 and pandemic-like avian H5N1 strains. In contrast, influenza split virus vaccines had a low ability to activate DC, regardless which strain was investigated. We also observed that whole virus vaccines stimulated virus-specific CD8+ memory T cells much stronger compared to split virus counterparts, whereas both vaccine formats activated CD4+ Th cell responses similarly. Moreover, our data showed that whole virus vaccine material is delivered into the cytosolic pathway of DC for effective activation of virus-specific CD8+ T cells. We conclude that vaccines against seasonal and pandemic (-like) influenza strains that aim to stimulate cross-reacting CD8+ T cells should include whole virus rather than split virus formulations.

Show MeSH
Related in: MedlinePlus