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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

Ex vivo interferon γ enzyme-linked immunosorbent spot assay responses tonucleoprotein (NP) and matrix protein 1 (M1). The graph represents the summedresponse to NP and M1 antigens in vaccinees (circles) and controls (squares) at therelevant time points; lines represent the median per group and open symbolsrepresent subjects who developed laboratory-confirmed influenza. Control subjectswere not assayed at day 0 or day 21. Vaccination took place on day 0 and influenzachallenge on day 30. Data were analyzed with a Kruskal-Wallis 1-way analysis ofvariance with selected pairs of data analyzed with a Dunn positive test. Nosignificant difference between the median response in the vaccinated and controlgroup was observed at time of screening (day 0 for vaccinees, day 29 for controls).A significant increase in the response was observed in vaccinees between days 0 and21 and days 0 and 29 (P < .001,P < .05, respectively). A significant differencebetween vaccinees and controls was observed at day 29(P < .05). Abbreviations: PBMC, peripheral bloodmononuclear cell; SFU, spot-forming units.
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CIS327F1: Ex vivo interferon γ enzyme-linked immunosorbent spot assay responses tonucleoprotein (NP) and matrix protein 1 (M1). The graph represents the summedresponse to NP and M1 antigens in vaccinees (circles) and controls (squares) at therelevant time points; lines represent the median per group and open symbolsrepresent subjects who developed laboratory-confirmed influenza. Control subjectswere not assayed at day 0 or day 21. Vaccination took place on day 0 and influenzachallenge on day 30. Data were analyzed with a Kruskal-Wallis 1-way analysis ofvariance with selected pairs of data analyzed with a Dunn positive test. Nosignificant difference between the median response in the vaccinated and controlgroup was observed at time of screening (day 0 for vaccinees, day 29 for controls).A significant increase in the response was observed in vaccinees between days 0 and21 and days 0 and 29 (P < .001,P < .05, respectively). A significant differencebetween vaccinees and controls was observed at day 29(P < .05). Abbreviations: PBMC, peripheral bloodmononuclear cell; SFU, spot-forming units.

Mentions: T-cell responses to the influenza antigens NP and M1 were measured in all volunteers atscreening and again on day of vaccination and 21 days later in the vaccinees and in allvolunteers on the day prior to challenge, as well as 8 occasions after influenza challenge(Figure 1). As previously observed[7], there was a clearly detectable responsein all volunteers at the time of screening, with a median response of 258 SFUs permillion PBMCs in the group who went on to receive the vaccine and 300 SFUs permillion PBMCs in the controls. The level of response was stable prior to vaccination,significantly boosted to 980 SFUs per million PBMCs 21 days after vaccination(P < .001 vs day 0) and then declined to 627 SFUs permillion PBMCs 8 days later (the day prior to influenza challenge,P < .05 vs day 0). The response in the control groupremained stable prior to influenza challenge, with a median of 215 SFUs per millionPBMCs measured on the day prior to influenza challenge (day 29). Although there was nosignificant difference in the responses between the 2 groups at screening, responses to NPand M1 at day 29 were significantly higher in the vaccinees compared to controls(P < .05) (Figure 1). Figure 1.


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)

Ex vivo interferon γ enzyme-linked immunosorbent spot assay responses tonucleoprotein (NP) and matrix protein 1 (M1). The graph represents the summedresponse to NP and M1 antigens in vaccinees (circles) and controls (squares) at therelevant time points; lines represent the median per group and open symbolsrepresent subjects who developed laboratory-confirmed influenza. Control subjectswere not assayed at day 0 or day 21. Vaccination took place on day 0 and influenzachallenge on day 30. Data were analyzed with a Kruskal-Wallis 1-way analysis ofvariance with selected pairs of data analyzed with a Dunn positive test. Nosignificant difference between the median response in the vaccinated and controlgroup was observed at time of screening (day 0 for vaccinees, day 29 for controls).A significant increase in the response was observed in vaccinees between days 0 and21 and days 0 and 29 (P < .001,P < .05, respectively). A significant differencebetween vaccinees and controls was observed at day 29(P < .05). Abbreviations: PBMC, peripheral bloodmononuclear cell; SFU, spot-forming units.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

CIS327F1: Ex vivo interferon γ enzyme-linked immunosorbent spot assay responses tonucleoprotein (NP) and matrix protein 1 (M1). The graph represents the summedresponse to NP and M1 antigens in vaccinees (circles) and controls (squares) at therelevant time points; lines represent the median per group and open symbolsrepresent subjects who developed laboratory-confirmed influenza. Control subjectswere not assayed at day 0 or day 21. Vaccination took place on day 0 and influenzachallenge on day 30. Data were analyzed with a Kruskal-Wallis 1-way analysis ofvariance with selected pairs of data analyzed with a Dunn positive test. Nosignificant difference between the median response in the vaccinated and controlgroup was observed at time of screening (day 0 for vaccinees, day 29 for controls).A significant increase in the response was observed in vaccinees between days 0 and21 and days 0 and 29 (P < .001,P < .05, respectively). A significant differencebetween vaccinees and controls was observed at day 29(P < .05). Abbreviations: PBMC, peripheral bloodmononuclear cell; SFU, spot-forming units.
Mentions: T-cell responses to the influenza antigens NP and M1 were measured in all volunteers atscreening and again on day of vaccination and 21 days later in the vaccinees and in allvolunteers on the day prior to challenge, as well as 8 occasions after influenza challenge(Figure 1). As previously observed[7], there was a clearly detectable responsein all volunteers at the time of screening, with a median response of 258 SFUs permillion PBMCs in the group who went on to receive the vaccine and 300 SFUs permillion PBMCs in the controls. The level of response was stable prior to vaccination,significantly boosted to 980 SFUs per million PBMCs 21 days after vaccination(P < .001 vs day 0) and then declined to 627 SFUs permillion PBMCs 8 days later (the day prior to influenza challenge,P < .05 vs day 0). The response in the control groupremained stable prior to influenza challenge, with a median of 215 SFUs per millionPBMCs measured on the day prior to influenza challenge (day 29). Although there was nosignificant difference in the responses between the 2 groups at screening, responses to NPand M1 at day 29 were significantly higher in the vaccinees compared to controls(P < .05) (Figure 1). Figure 1.

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