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Preliminary assessment of the efficacy of a T-cell-based influenza vaccine, MVA-NP+M1, in humans.

Lillie PJ, Berthoud TK, Powell TJ, Lambe T, Mullarkey C, Spencer AJ, Hamill M, Peng Y, Blais ME, Duncan CJ, Sheehy SH, Havelock T, Faust SN, Williams RL, Gilbert A, Oxford J, Dong T, Hill AV, Gilbert SC - Clin. Infect. Dis. (2012)

Bottom Line: Volunteers had a significantly increased T-cell response to the vaccine antigens following a single dose of the vaccine, with an increase in cytolytic effector molecules.This study provides the first demonstration of clinical efficacy of a T-cell-based influenza vaccine and indicates that further clinical development should be undertaken.NCT00993083.

View Article: PubMed Central - PubMed

Affiliation: Jenner Institute, University of Oxford, UK.

ABSTRACT

Background: The novel influenza vaccine MVA-NP+M1 is designed to boost cross-reactive T-cell responses to internal antigens of the influenza A virus that are conserved across all subtypes, providing protection against both influenza disease and virus shedding against all influenza A viruses. Following a phase 1 clinical study that demonstrated vaccine safety and immunogenicity, a phase 2a vaccination and influenza challenge study has been conducted in healthy adult volunteers.

Methods: Volunteers with no measurable serum antibodies to influenza A/Wisconsin/67/2005 received either a single vaccination with MVA-NP+M1 or no vaccination. T-cell responses to the vaccine antigens were measured at enrollment and again prior to virus challenge. All volunteers underwent intranasal administration of influenza A/Wisconsin/67/2005 while in a quarantine unit and were monitored for symptoms of influenza disease and virus shedding.

Results: Volunteers had a significantly increased T-cell response to the vaccine antigens following a single dose of the vaccine, with an increase in cytolytic effector molecules. Intranasal influenza challenge was undertaken without safety issues. Two of 11 vaccinees and 5 of 11 control subjects developed laboratory-confirmed influenza (symptoms plus virus shedding). Symptoms of influenza were less pronounced in the vaccinees and there was a significant reduction in the number of days of virus shedding in those vaccinees who developed influenza (mean, 1.09 days in controls, 0.45 days in vaccinees, P = .036).

Conclusions: This study provides the first demonstration of clinical efficacy of a T-cell-based influenza vaccine and indicates that further clinical development should be undertaken.

Clinical trials registration: NCT00993083.

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Related in: MedlinePlus

Responses to M158–66 in human leukocyte antigenA2–positive volunteers. Whole blood drawn 1 day prior to virus challenge waslabeled for tetramer (A*0201/GILGFVFTL) followed by perforin or granzyme Astaining. Values shown are the percentage of CD8+ T cells orTet+ cells; individuals are shown as a single point with linesrepresenting the median per group. Open symbols represent samples from volunteerswho subsequently developed laboratory-confirmed influenza. For each marker the datawere analyzed with an unpaired t test; P valuesare shown for statistically significant differences between vaccinees andcontrols.
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CIS327F2: Responses to M158–66 in human leukocyte antigenA2–positive volunteers. Whole blood drawn 1 day prior to virus challenge waslabeled for tetramer (A*0201/GILGFVFTL) followed by perforin or granzyme Astaining. Values shown are the percentage of CD8+ T cells orTet+ cells; individuals are shown as a single point with linesrepresenting the median per group. Open symbols represent samples from volunteerswho subsequently developed laboratory-confirmed influenza. For each marker the datawere analyzed with an unpaired t test; P valuesare shown for statistically significant differences between vaccinees andcontrols.

Mentions: Six of the vaccinees and 7 of the controls were positive for human leukocyte antigenA*0201 and therefore likely to have preexisting T-cell responses to the knownA2-restricted immunodominant epitope M158–66. A tetramer for this epitopewas used to measure phenotypic markers in PBMCs from these volunteers. A significantdifference between vaccinated and control donors on the day prior to influenza challengewas observed in the expression of the cytotoxic markers perforin (D48 epitope [8]) and granzyme A (Figure 2), indicating that the antigen-specificCD8+ T cells in the vaccinees were more highly activated than T cellsfrom the control donors. Figure 2.


Preliminary assessment of the efficacy of a T-cell-based influenza vaccine, MVA-NP+M1, in humans.

Lillie PJ, Berthoud TK, Powell TJ, Lambe T, Mullarkey C, Spencer AJ, Hamill M, Peng Y, Blais ME, Duncan CJ, Sheehy SH, Havelock T, Faust SN, Williams RL, Gilbert A, Oxford J, Dong T, Hill AV, Gilbert SC - Clin. Infect. Dis. (2012)

Responses to M158–66 in human leukocyte antigenA2–positive volunteers. Whole blood drawn 1 day prior to virus challenge waslabeled for tetramer (A*0201/GILGFVFTL) followed by perforin or granzyme Astaining. Values shown are the percentage of CD8+ T cells orTet+ cells; individuals are shown as a single point with linesrepresenting the median per group. Open symbols represent samples from volunteerswho subsequently developed laboratory-confirmed influenza. For each marker the datawere analyzed with an unpaired t test; P valuesare shown for statistically significant differences between vaccinees andcontrols.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3369564&req=5

CIS327F2: Responses to M158–66 in human leukocyte antigenA2–positive volunteers. Whole blood drawn 1 day prior to virus challenge waslabeled for tetramer (A*0201/GILGFVFTL) followed by perforin or granzyme Astaining. Values shown are the percentage of CD8+ T cells orTet+ cells; individuals are shown as a single point with linesrepresenting the median per group. Open symbols represent samples from volunteerswho subsequently developed laboratory-confirmed influenza. For each marker the datawere analyzed with an unpaired t test; P valuesare shown for statistically significant differences between vaccinees andcontrols.
Mentions: Six of the vaccinees and 7 of the controls were positive for human leukocyte antigenA*0201 and therefore likely to have preexisting T-cell responses to the knownA2-restricted immunodominant epitope M158–66. A tetramer for this epitopewas used to measure phenotypic markers in PBMCs from these volunteers. A significantdifference between vaccinated and control donors on the day prior to influenza challengewas observed in the expression of the cytotoxic markers perforin (D48 epitope [8]) and granzyme A (Figure 2), indicating that the antigen-specificCD8+ T cells in the vaccinees were more highly activated than T cellsfrom the control donors. Figure 2.

Bottom Line: Volunteers had a significantly increased T-cell response to the vaccine antigens following a single dose of the vaccine, with an increase in cytolytic effector molecules.This study provides the first demonstration of clinical efficacy of a T-cell-based influenza vaccine and indicates that further clinical development should be undertaken.NCT00993083.

View Article: PubMed Central - PubMed

Affiliation: Jenner Institute, University of Oxford, UK.

ABSTRACT

Background: The novel influenza vaccine MVA-NP+M1 is designed to boost cross-reactive T-cell responses to internal antigens of the influenza A virus that are conserved across all subtypes, providing protection against both influenza disease and virus shedding against all influenza A viruses. Following a phase 1 clinical study that demonstrated vaccine safety and immunogenicity, a phase 2a vaccination and influenza challenge study has been conducted in healthy adult volunteers.

Methods: Volunteers with no measurable serum antibodies to influenza A/Wisconsin/67/2005 received either a single vaccination with MVA-NP+M1 or no vaccination. T-cell responses to the vaccine antigens were measured at enrollment and again prior to virus challenge. All volunteers underwent intranasal administration of influenza A/Wisconsin/67/2005 while in a quarantine unit and were monitored for symptoms of influenza disease and virus shedding.

Results: Volunteers had a significantly increased T-cell response to the vaccine antigens following a single dose of the vaccine, with an increase in cytolytic effector molecules. Intranasal influenza challenge was undertaken without safety issues. Two of 11 vaccinees and 5 of 11 control subjects developed laboratory-confirmed influenza (symptoms plus virus shedding). Symptoms of influenza were less pronounced in the vaccinees and there was a significant reduction in the number of days of virus shedding in those vaccinees who developed influenza (mean, 1.09 days in controls, 0.45 days in vaccinees, P = .036).

Conclusions: This study provides the first demonstration of clinical efficacy of a T-cell-based influenza vaccine and indicates that further clinical development should be undertaken.

Clinical trials registration: NCT00993083.

Show MeSH
Related in: MedlinePlus