PowderMed has submitted regulatory documentation to the UK Medicines and Healthcare Products Regulatory Agency (MHRA) for permission to conduct a clinical trial to test its H5N1 avian flu vaccine
It is planned that the trial will be conducted at a clinical research unit in London.
This new vaccine is based upon PowderMed's proprietary system for delivering DNA vaccines - it is a needle-free injection device that fires gold particles coated with DNA (encoding genes specific to the flu strain) at supersonic speed into the immune cells of the skin.
This first-time-in-man clinical trial will examine the ability of a vaccine based upon the Vietnam H5N1 avian influenza strain to protect against a potential pandemic form of flu.
A previous study, conducted by PowderMed in the United States, demonstrated that this vaccine technology was able to produce 100% protective immune responses in adult volunteers to a vaccine which encoded an annual influenza strain.
Using bird flu strains this vaccine has also shown 100% protection in various experimental models.
John Beadle, PowderMed's chief medical officer, stated that "This is an exciting opportunity for PowderMed to conduct the first clinical trial on a vaccine which may have a very important role in the event of a future pandemic.
"We have selected this particular clinical unit in London to conduct the study because they are currently building up a database of volunteers for future influenza studies.
"This will allow us to conduct the study and get the results as quickly as possible once we have regulatory approval".
Clive Dix, CEO of PowderMed, added: "Our approach provides a rapid route to vaccine development that can be applied to existing and emerging flu strains including, for example, the threat posed by a pandemic flu strain.
"DNA vaccines have a huge potential to limit the burden of disease and can be manufactured very rapidly, in large amounts: enough to vaccinate the whole of the UK population twice over (prime and boost) requires just 1kg of DNA and can be manufactured and available in just three months from the point a strain is identified.
"We are very excited to see both our annual and pandemic influenza programmes progress through clinical development".
PowderMed is a private immunotherapeutic company based in Oxford, UK.
The company is focused on the clinical development and manufacture of therapeutic and prophylactic DNA-based vaccines for viral diseases and cancer.
The company has four clinical and three pre-clinical stage projects.
The lead clinical programme has shown positive Phase I results in the treatment and prevention of human influenza.
This technology is uniquely and easily adaptable to treat avian flu and to address the pandemic threat.
PowderMed also has a product for the treatment of genital herpes in Phase I trials, and two partnered Phase I programmes in cancer (Ludwig Institute) and HIV/Aids (Glaxo SmithKline).
PowderMed vaccines are delivered using PMED (particle mediated epidermal delivery), a needle-free, virtually painless delivery system that requires minimal medical training, allows self-administration and requires no refrigeration for stockpiling.
Specifically, PowderMed's technology delivers DNA to the epidermal layer of the skin where it is presented to the cells of the immune network, thereby creating immunity and thus facilitating both treatment and prevention of disease.
PowderMed's influenza vaccines.
PowderMed's DNA vaccines are made up of two components - the vaccine-specific DNA and the delivery device.
This approach provides a rapid route to vaccine development that can be applied to existing and emerging flu strains including, for example, the threat of the emergence of a pandemic flu strain.
PowderMed has two flu vaccines in development for annual and avian flu (H3 and H5 strains).
Results of previous preclinical and clinical testing of PowderMed's DNA-based influenza vaccines, including H3 and pandemic H5 strains utilising PMED, show consistent and robust immune responses in animals and humans at micro-gram doses.
The DNA vaccine consists of the standard DNA backbone with an immunologically active gene specific to each viral strain - the gene cassette.
The delivery device is a fully developed and patented system, called Particle Mediated Epidermal Delivery (PMED), whereby gold particles coated in the vaccine DNA are propelled into the skin using high-pressure helium (see below).
In this way, vaccine DNA is delivered directly to cells of the immune network in the skin, thereby stimulating immunity.
PowderMed's annual flu vaccine uses the gene encoding for the protein of the H3/Panama strain.
In the case of the Avian flu vaccine, the H5 Vietnam gene cassette is used.
This gene is specific to current Avian flu and encodes part of the flu virus's protein shell.
When the vaccine is administered, into the surface of the skin, the H5 gene is expressed to produce the virus protein.
This harnesses the individual's immune system to mount an immune response against the protein, such that, in the event of later exposure to actual Avian flu virus, the immune system will be able to destroy the flu virus and thus provide protection.
Using PowderMed's technology, vaccination is needle free, virtually painless, can be easily administered without the need for trained medical personnel and it can be stored at room temperature making it ideal for large volume stockpiling and distribution.
The company has developed a full clinical trial and manufacturing strategy that anticipates the demands that Governments may have for both annual influenza vaccine and a pandemic flu vaccine.
Background to influenza.
Flu is an acute viral infection of the respiratory tract caused by the Influenza virus.
There are many different subtypes or strains of Influenza viruses, differentiated by proteins on the surface of the virus: the hemagglutinin or HA protein and the neuraminidase or NA protein.
So far, 15 H and nine N subtypes have been identified.
These viruses continually change over time and every year small modifications (antigenic drifts) are responsible for seasonal outbreaks or epidemics of influenza.
Worldwide, an estimated 100,000 hospitalisations and about 20,000 deaths occur each year from the flu or its complications (source: the National Institute of Allergy and Infectious Diseases).
Abrupt genetic recombinations of HA and/or NA proteins on the surface of the virus (antigenic shifts) result in the emergence of a new virus, which is a key step towards a pandemic strain.
To date, there is little evidence that the H5N1 virus (associated with avian flu) is capable of spreading from human to human, a pre-requisite for a pandemic strain, but should recombination (antigenic shift) of H5N1 occur, this strain could become responsible for a global outbreak of the disease or pandemic, with high levels of illness and death.
The WHO (World Health Organization) has reported 97 human cases of avian flu since 26 December 2003.
Since that date 53 deaths have been reported.
Previous influenza pandemics:.
1918-1919 'Spanish flu' (H1N1) with up to 50 millions deaths worldwide.
1957-1958 Asian flu' (H2N2) caused about 70,000 deaths in the USA.
1968-1969 'Hong Kong flu' (H3N2) caused about 34,000 deaths in the USA.
Both the 1957-1958 and the 1968-1969 pandemics were caused by viruses containing combinations of human and avian Influenza viruses.
Particle mediated epidermal delivery (PMED) technology.
Using the PMED device, DNA precipitated onto microscopic gold particles is propelled by pressurised helium gas at near supersonic speeds into the epidermis.
The microscopic gold particles (mean particle diameter 1-3 microns) are used as the carrier because they have the appropriate size and density needed to deliver the DNA directly into the immunologically active antigen presenting cells (APCs) of the epidermis.
These cells have a mean diameter of 20microns and thus the microscopic gold can easily enter the cell.
Studies have shown that once inside the nuclei of APCs, the DNA elutes off the gold and becomes transcriptionally active, producing the encoded protein that, when presented by the APCs to lymphocytes, triggers strong T-cell mediated immune responses.
It is this ability of PMED to produce a robust and reproducible T-cell mediated immune response to a broad range of viral and cancer antigens, that provides PowderMed with its unique competitive advantage in the field of DNA-based vaccines.
