Ignite Creation Date:
2024-05-05 @ 9:42 PM
Last Modification Date:
2024-10-26 @ 10:08 AM
Study NCT ID:
NCT00942071
Status:
COMPLETED
Last Update Posted:
2012-11-29
First Post:
2009-07-16
Brief Title:
A Study to Assess the Safety and Immunogenicity of a New Influenza Vaccine Candidate MVA-NPM1 in Healthy Adults
Sponsor:
University of Oxford
Organization:
University of Oxford
Study Overview
Official Title:
A Phase I Study to Assess the Safety and Immunogenicity of a New Influenza Vaccine Candidate MVA-NPM1 in Healthy Adults
Status:
COMPLETED
Status Verified Date:
2012-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is an open label phase I study to assess the safety of a novel influenza vaccine MVA-NPM1 All volunteers recruited will be healthy Twelve volunteers will be administered with a single dose of 5 x 107 pfu of MVA-NPM1 via the Intradermal ID route group 1 Sixteen volunteers will receive Intramuscular IM MVA-NPM1 The first 8 volunteers will be administered a single dose of 5 x 107 pfu of MVA-NPM1 followed by a further eight receiving 25 x 108 pfu of MVA-NPM1 group 2 The 3rd group will be split into 3 groups of 10 volunteers in the age ranges 50-59 60-69 and 70 and above and administered intramuscularly with a single dose of 15 x 108 pfu of MVA-NPM1 Safety data will be collected The secondary aim of this study will be to assess the cellular immune responses generated by each dose
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
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None