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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

Total of symptom scores at each time point following challenge(A) or total grade 2 and 3 symptom and examination scores(B) for vaccinees (circles) and controls (squares), with thegroup mean indicated by a line. Open symbols denote subjects who developedlaboratory-confirmed influenza after challenge.
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CIS327F3: Total of symptom scores at each time point following challenge(A) or total grade 2 and 3 symptom and examination scores(B) for vaccinees (circles) and controls (squares), with thegroup mean indicated by a line. Open symbols denote subjects who developedlaboratory-confirmed influenza after challenge.

Mentions: The primary outcome of the challenge study was the number of subjects in each groupdiagnosed with laboratory-confirmed influenza, defined as mild or moderate/severe symptomsof influenza infection plus laboratory detection of influenza virus in any of the dailynasal washes conducted following influenza challenge (Table 1). In total, 2 vaccinees and 5 controls developedlaboratory-confirmed influenza. Of these, 1 vaccinee and 4 controls experienced moderateto severe symptoms in addition to virus shedding. Comparing the vaccinated and controlgroups as a whole, symptoms were fewer in vaccinees at all time points following influenzachallenge (Figure 3A),with symptoms peaking on the second and third days. Vaccinees as a group experienced asignificant reduction in the number of days of virus shedding in the presence oflaboratory-confirmed influenza (5 of 55 days in vaccinees and 12 of 55 days in controls;P = .036). Table 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)

Total of symptom scores at each time point following challenge(A) or total grade 2 and 3 symptom and examination scores(B) for vaccinees (circles) and controls (squares), with thegroup mean indicated by a line. Open symbols denote subjects who developedlaboratory-confirmed influenza after challenge.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

CIS327F3: Total of symptom scores at each time point following challenge(A) or total grade 2 and 3 symptom and examination scores(B) for vaccinees (circles) and controls (squares), with thegroup mean indicated by a line. Open symbols denote subjects who developedlaboratory-confirmed influenza after challenge.
Mentions: The primary outcome of the challenge study was the number of subjects in each groupdiagnosed with laboratory-confirmed influenza, defined as mild or moderate/severe symptomsof influenza infection plus laboratory detection of influenza virus in any of the dailynasal washes conducted following influenza challenge (Table 1). In total, 2 vaccinees and 5 controls developedlaboratory-confirmed influenza. Of these, 1 vaccinee and 4 controls experienced moderateto severe symptoms in addition to virus shedding. Comparing the vaccinated and controlgroups as a whole, symptoms were fewer in vaccinees at all time points following influenzachallenge (Figure 3A),with symptoms peaking on the second and third days. Vaccinees as a group experienced asignificant reduction in the number of days of virus shedding in the presence oflaboratory-confirmed influenza (5 of 55 days in vaccinees and 12 of 55 days in controls;P = .036). Table 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