A single vaccination with MVA-NP+M1 boosts T-cell responses to conserved influenza
antigens in humans. Protection against influenza disease and virus shedding was
demonstrated in an influenza virus challenge study.
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.