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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

CONSORT flow diagram of the clinical trial.
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pone-0062778-g001: CONSORT flow diagram of the clinical trial.

Mentions: The CONSORT flow chart for the trial is shown in figure 1. Beginning 27 July 2009, an MVA vaccine [17] expressing influenza (H3N2 A/Panama/2007/99) NP+M1 was administered, 1.5×108 plaque-forming units (PFUs), to 11 human volunteers 1 month before challenge with influenza (H3N2 A/Wisconsin/67/2005). Control subjects were challenged with H3N2 virus only. The viral challenge study was conducted by Retroscreen Virology Ltd [16]. Symptoms and virus shedding were monitored. Differences between IFN-γ ELISPOT analysis pre and post challenge are given in [16]. To examine the acute response after virus infection, blood was taken one day before (−1) and days 4 and 7 after challenge, transported to Oxford and then flow cytometry performed on whole blood.


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)

CONSORT flow diagram of the clinical trial.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0062778-g001: CONSORT flow diagram of the clinical trial.
Mentions: The CONSORT flow chart for the trial is shown in figure 1. Beginning 27 July 2009, an MVA vaccine [17] expressing influenza (H3N2 A/Panama/2007/99) NP+M1 was administered, 1.5×108 plaque-forming units (PFUs), to 11 human volunteers 1 month before challenge with influenza (H3N2 A/Wisconsin/67/2005). Control subjects were challenged with H3N2 virus only. The viral challenge study was conducted by Retroscreen Virology Ltd [16]. Symptoms and virus shedding were monitored. Differences between IFN-γ ELISPOT analysis pre and post challenge are given in [16]. To examine the acute response after virus infection, blood was taken one day before (−1) and days 4 and 7 after challenge, transported to Oxford and then flow cytometry performed on whole blood.

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