A Study to Assess the Safety and Efficacy of a New Influenza Candidate Vaccine MVA-NP+M1 In Healthy Adults
This is a Phase IIa open label, non placebo controlled, non-randomised controlled challenge study. The primary objective of this study is to assess the safety of a new influenza vaccine, MVA-NP+M1, when administered as a single dose to healthy volunteers.
Initially two volunteers will be vaccinated and challenged with Influenza, followed by vaccination of a further 12 volunteers and an Influenza challenge of those 12 along with 12 non-vaccinated controls.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||A Phase IIA Study to Assess the Safety and Efficacy of a New Influenza Candidate Vaccine MVA-NP+M1 In Healthy Adults|
- Safety of a new Influenza vaccine, MVA-NP+M1, when administered to healthy volunteers [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
- Cellular immune response generated by a new influenza vaccine MVA- NP+M1 when administered as a single dose to healthy adults. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
|Study Start Date:||June 2009|
|Study Completion Date:||March 2010|
|Primary Completion Date:||March 2010 (Final data collection date for primary outcome measure)|
14 volunteers (2 in lead safety group and 12 in main study group) to receive MVA-NP+M1 via the IM route. Volunteers will then be challenged with Influenza 30 days post vaccination.
Intramuscular injection at 1.5 x 10^8 pfu/ml at day 0
No Intervention: Control
12 volunteers who will not receive vaccine but will also be challenged with Influenza on day 30
Antibodies against the external proteins of influenza can prevent the virus from infecting cells and either prevent infection or limit the spread of infection. However the surface proteins are highly variable and there is little antibody cross-reactivity between variants. Once a cell has been infected with the virus, it is then vulnerable to T cell attack resulting in the destruction of infected cells so that no more virus can be produced and the infection is controlled. There is evidence from clinical trials of influenza challenge, and animal models that T cell responses can protect in the absence of antibodies. Additionally, since T cells can recognise the highly conserved internal proteins of influenza, cross-subtype protection can be achieved.
Seasonal influenza infection results in a T cell response to the virus which can protect against subsequent infection. However over the course of a few years these responses decline below protective levels. The new vaccine being tested in this study is designed to boost these T cell responses back to protective levels. Even responses that may be too low to be reliably quantified by currently available assays may still be boosted to high levels by a single dose of recombinant MVA. Since the internal proteins vary little between influenza subtypes, this could result in a 'universal' vaccine against influenza A. If the need to continually reformulate the vaccine in response to mutations in the viral coat proteins can be removed, the universal vaccine could be produced in large amounts and used more widely than the existing seasonal 'flu vaccines, thus protecting the population against currently circulating viruses and new virus types that are at present only found in avian species.
There is very little polymorphism of NP and M1 between influenza A isolates. NP is 92% identical between H3N2 and H1N1 strains, and 91% identical between H3N2 and H5N1 strains. M1 is 95% identical between H3N2 and H1N1 strains, and 93% identical between H3N2 and H5N1 strains. This low level of variation appears to allow strong T cell cross-reactivity.
MVA is a highly attenuated strain of vaccinia virus that is unable to replicate efficiently in human cell lines and most mammalian cells. Viral replication is blocked at a late stage of virion assembly, so, importantly, viral and recombinant protein synthesis is unimpaired. This means that MVA is an efficient single round expression vector, incapable of causing infection in mammals. Replication-deficient recombinant MVA has been seen as an exceptionally safe viral vector. This safety in man is consistent with the avirulence of MVA in animal models, where recombinant MVAs have also been shown to be protectively immunogenic as vaccines against viral diseases and cancer. Importantly for a vaccine which may eventually be used in a large proportion of the population, recombinant MVAs expressing HIV antigens have been shown to be safe and immunogenic in HIV-infected subjects.
|Wellcome Trust Clinical Research Facility, University of Southampton|
|Southampton, Hampshire, United Kingdom, SO16 6YD|
|Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital|
|Oxford, Oxfordshire, United Kingdom, OX3 7LJ|
|Principal Investigator:||Adrian VS Hill, DPhil||University of Oxford|