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Examination of influenza specific T cell responses after influenza virus challenge in individuals vaccinated with MVA-NP+M1 vaccine.

Powell TJ, Peng Y, Berthoud TK, Blais ME, Lillie PJ, Hill AV, Rowland-Jones SL, McMichael AJ, Gilbert SC, Dong T - PLoS ONE (2013)

Bottom Line: A potential strategy is to induce CD8(+) and CD4(+) T cells that recognize epitopes within internal proteins that are less subject to antigenic drift.Augmenting humoral responses to HA with T cell responses to more conserved antigens may result in a more broadly protective vaccine.These data indicate that antigen specific T cells are a useful additional measure for use in human vaccination or immunization studies.

View Article: PubMed Central - PubMed

Affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom. timothy.powell@imm.ox.ac.uk

ABSTRACT
Current influenza vaccines stimulate neutralising antibody to the haemagglutinin antigen but as there is antigenic drift in HA it is difficult to prepare a vaccine in advance against an emergent strain. A potential strategy is to induce CD8(+) and CD4(+) T cells that recognize epitopes within internal proteins that are less subject to antigenic drift. Augmenting humoral responses to HA with T cell responses to more conserved antigens may result in a more broadly protective vaccine. In this study, we evaluate the quality of influenza specific T cell responses in a clinical trial using MVA-NP+M1 vaccination followed by influenza virus challenge. In vaccinated volunteers, the expression of Granzyme A, Perforin and CD57 on influenza HLA A*02 M158-66 antigen specific cells was higher than non-vaccinated volunteers before and after challenge despite a similar frequency of antigen specific cells. BCL2 expression was lower in vaccinated volunteers. These data indicate that antigen specific T cells are a useful additional measure for use in human vaccination or immunization studies.

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Related in: MedlinePlus

Surface and intracellular activation markers are enhanced on tetramer labeled cells from vaccinated donors compared to control.A) Time course between day −1 and 7 and expression of noted markers on M158–66 tetramer labeled cells. B) Representative flow cytometry plot of M158–66 tetramer positive cells labeled for CD27 and CD28 on day −1 showing similar profiles. C) Graphs plot the percentage of tetramer+ cells or MFI of tetramer+ cells with the noted markers. D) Representative flow cytometry plot of two donors showing control (open plot) and vaccinated volunteer (filled histogram) labeled with anti-D48 Pfp on day 4. Groups were compared using repeated measures ANOVA.
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pone-0062778-g003: Surface and intracellular activation markers are enhanced on tetramer labeled cells from vaccinated donors compared to control.A) Time course between day −1 and 7 and expression of noted markers on M158–66 tetramer labeled cells. B) Representative flow cytometry plot of M158–66 tetramer positive cells labeled for CD27 and CD28 on day −1 showing similar profiles. C) Graphs plot the percentage of tetramer+ cells or MFI of tetramer+ cells with the noted markers. D) Representative flow cytometry plot of two donors showing control (open plot) and vaccinated volunteer (filled histogram) labeled with anti-D48 Pfp on day 4. Groups were compared using repeated measures ANOVA.

Mentions: Since the number or proportion of antigen specific cells was not different between the groups we then examined the cell surface and intracellular phenotype of the M158–66 CD8+ T cells. We examined the expression of CD27, CD28, CD38 and HLA-DR on the surface of the cells that are markers associated with activation and differentiation [19]. We found that the expression of CD27, CD28, CD38 and HLA-DR were not different between vaccinated and control donors by repeated measures ANOVA (figure 3A). The levels of CD57, which is a marker associated with either senescence or activation were different by repeated measures ANOVA (p = **0.00705) and CD57 was enhanced on cells from vaccinated volunteers. Double CD27+ CD28+ positive cells were not different between the groups and a representative flow cytometry profile is shown in figure 3B.


Examination of influenza specific T cell responses after influenza virus challenge in individuals vaccinated with MVA-NP+M1 vaccine.

Powell TJ, Peng Y, Berthoud TK, Blais ME, Lillie PJ, Hill AV, Rowland-Jones SL, McMichael AJ, Gilbert SC, Dong T - PLoS ONE (2013)

Surface and intracellular activation markers are enhanced on tetramer labeled cells from vaccinated donors compared to control.A) Time course between day −1 and 7 and expression of noted markers on M158–66 tetramer labeled cells. B) Representative flow cytometry plot of M158–66 tetramer positive cells labeled for CD27 and CD28 on day −1 showing similar profiles. C) Graphs plot the percentage of tetramer+ cells or MFI of tetramer+ cells with the noted markers. D) Representative flow cytometry plot of two donors showing control (open plot) and vaccinated volunteer (filled histogram) labeled with anti-D48 Pfp on day 4. Groups were compared using repeated measures ANOVA.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3643913&req=5

pone-0062778-g003: Surface and intracellular activation markers are enhanced on tetramer labeled cells from vaccinated donors compared to control.A) Time course between day −1 and 7 and expression of noted markers on M158–66 tetramer labeled cells. B) Representative flow cytometry plot of M158–66 tetramer positive cells labeled for CD27 and CD28 on day −1 showing similar profiles. C) Graphs plot the percentage of tetramer+ cells or MFI of tetramer+ cells with the noted markers. D) Representative flow cytometry plot of two donors showing control (open plot) and vaccinated volunteer (filled histogram) labeled with anti-D48 Pfp on day 4. Groups were compared using repeated measures ANOVA.
Mentions: Since the number or proportion of antigen specific cells was not different between the groups we then examined the cell surface and intracellular phenotype of the M158–66 CD8+ T cells. We examined the expression of CD27, CD28, CD38 and HLA-DR on the surface of the cells that are markers associated with activation and differentiation [19]. We found that the expression of CD27, CD28, CD38 and HLA-DR were not different between vaccinated and control donors by repeated measures ANOVA (figure 3A). The levels of CD57, which is a marker associated with either senescence or activation were different by repeated measures ANOVA (p = **0.00705) and CD57 was enhanced on cells from vaccinated volunteers. Double CD27+ CD28+ positive cells were not different between the groups and a representative flow cytometry profile is shown in figure 3B.

Bottom Line: A potential strategy is to induce CD8(+) and CD4(+) T cells that recognize epitopes within internal proteins that are less subject to antigenic drift.Augmenting humoral responses to HA with T cell responses to more conserved antigens may result in a more broadly protective vaccine.These data indicate that antigen specific T cells are a useful additional measure for use in human vaccination or immunization studies.

View Article: PubMed Central - PubMed

Affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom. timothy.powell@imm.ox.ac.uk

ABSTRACT
Current influenza vaccines stimulate neutralising antibody to the haemagglutinin antigen but as there is antigenic drift in HA it is difficult to prepare a vaccine in advance against an emergent strain. A potential strategy is to induce CD8(+) and CD4(+) T cells that recognize epitopes within internal proteins that are less subject to antigenic drift. Augmenting humoral responses to HA with T cell responses to more conserved antigens may result in a more broadly protective vaccine. In this study, we evaluate the quality of influenza specific T cell responses in a clinical trial using MVA-NP+M1 vaccination followed by influenza virus challenge. In vaccinated volunteers, the expression of Granzyme A, Perforin and CD57 on influenza HLA A*02 M158-66 antigen specific cells was higher than non-vaccinated volunteers before and after challenge despite a similar frequency of antigen specific cells. BCL2 expression was lower in vaccinated volunteers. These data indicate that antigen specific T cells are a useful additional measure for use in human vaccination or immunization studies.

Show MeSH
Related in: MedlinePlus