A Study to Assess the Safety and Efficacy of a New Influenza Candidate Vaccine MVA-NP+M1 In Healthy Adults
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): MVA-NP+M1
Intervention type(s): Biological
Intervention description(s): Intramuscular injection at 1.5 x 10^8 pfu/ml at day 0
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Influenza; Vaccine