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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

Frequency of tetramer positive cells is similar between vaccinated and control volunteers.Data shows percentage of CD8 cells within a CD8 gate with vaccinated as closed squares and control open circles. B) Representative FACS profile of one vaccinated and one control donor at day −1, one day before challenge with influenza virus.
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pone-0062778-g002: Frequency of tetramer positive cells is similar between vaccinated and control volunteers.Data shows percentage of CD8 cells within a CD8 gate with vaccinated as closed squares and control open circles. B) Representative FACS profile of one vaccinated and one control donor at day −1, one day before challenge with influenza virus.

Mentions: Initially we analysed the percentage and absolute numbers of tetramer positive CD8+ T cells for each HLA-A*02 volunteer by FACS on the day before and up to day 7 post challenge. Surprisingly we found that the percentage of M158–66 specific cells, shown in Figure 2A, was not different between vaccinated and control donors. A representative flow cytometry profile from one vaccinated and one control donor is shown in figure 2B, which shows cells gated on CD8 and the percentage of tetramer positive cells within that gate. The absolute number of M158–66 antigen specific CD8+ T cells was also calculated using CD8 counts from the Trucount and these were not significantly different between groups (data not shown). Overall T cell responses to overlapping peptides spanning the entire H3N2 proteome [5] were tested and no significant differences were observed between vaccinated and control groups to most proteins, despite raised responses to NP in the vaccinated group before infection (figure S1) and [16], [17]. There is an overall trend of elevation of T cell responses in both groups 7 days after the challenge, which could mainly be CD4 dependent responses as described by Wilkinson et al., [21].


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)

Frequency of tetramer positive cells is similar between vaccinated and control volunteers.Data shows percentage of CD8 cells within a CD8 gate with vaccinated as closed squares and control open circles. B) Representative FACS profile of one vaccinated and one control donor at day −1, one day before challenge with influenza virus.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0062778-g002: Frequency of tetramer positive cells is similar between vaccinated and control volunteers.Data shows percentage of CD8 cells within a CD8 gate with vaccinated as closed squares and control open circles. B) Representative FACS profile of one vaccinated and one control donor at day −1, one day before challenge with influenza virus.
Mentions: Initially we analysed the percentage and absolute numbers of tetramer positive CD8+ T cells for each HLA-A*02 volunteer by FACS on the day before and up to day 7 post challenge. Surprisingly we found that the percentage of M158–66 specific cells, shown in Figure 2A, was not different between vaccinated and control donors. A representative flow cytometry profile from one vaccinated and one control donor is shown in figure 2B, which shows cells gated on CD8 and the percentage of tetramer positive cells within that gate. The absolute number of M158–66 antigen specific CD8+ T cells was also calculated using CD8 counts from the Trucount and these were not significantly different between groups (data not shown). Overall T cell responses to overlapping peptides spanning the entire H3N2 proteome [5] were tested and no significant differences were observed between vaccinated and control groups to most proteins, despite raised responses to NP in the vaccinated group before infection (figure S1) and [16], [17]. There is an overall trend of elevation of T cell responses in both groups 7 days after the challenge, which could mainly be CD4 dependent responses as described by Wilkinson et al., [21].

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