PowderMed: flying ahead in avian flu

PowderMed: flying ahead in avian flu

PowderMed has submitted an application to regulators seeking to conduct human trials of its avian influenza vaccine. Developing an effective vaccine against the next influenza pandemic is a challenging task, but one many companies are taking on. However, until a virus able to cause a pandemic emerges, no one knows for certain which product will be most effective.

PowderMed has applied to the 's Medicines and Healthcare Products Regulatory Agency (MHRA) for permission to conduct a clinical trial of its H5N1 vaccine, which uses PowderMed's proprietary needle-free system for delivering DNA vaccines.

If cleared by the regulator, this clinical trial will examine the ability of a vaccine based on the Vietnam H5N1 avian influenza strain to protect against a potentially pandemic form of flu.

Pre-pandemic period

The World Health Organization (WHO) believes the world is currently in a pre-pandemic period - a stage in which a new influenza subtype is causing disease in humans, but is not yet transmissible between humans. As of July 4, 2006, 229 human cases of H5N1 infection had been confirmed by the WHO, of which 131 resulted in death. In all but one case, infection is believed to have been transmitted from poultry to humans. While the mortality rate is currently 57%, the incidence of infection in man is still extremely low.

For the virus to be able to trigger a human pandemic, it must first mutate into a form that can be spread easily from one infected individual to the next. At present, the mutation that enables this has not yet occurred. While this prevents the pandemic, it hampers development of a cure or vaccine since the virus that will cause the next influenza pandemic does not yet exist. As a result, developing and testing treatments and prophylaxes is currently a speculative business.

Current influenza vaccine production relies on incubation in chicken eggs - a technique that is over 50 years old. The process is slow, difficult to scale up and prone to contamination, among other difficulties. As a result, there is a considerable time lag between the identification of new influenza strains and vaccine availability (between six and nine months for mass production).

The composition of the seasonal flu vaccine is modified every year to keep pace of the evolving virus. Each year, three strains that are expected to be prevalent the following winter are chosen for vaccine development.

Turning to DNA vaccines

Developing a vaccine to protect against H5N1 is more difficult, especially considering the increased speed with which it will spread. During the 1957 pandemic, the virus took four months to spread across and a further two months to reach the rest of the world. Identifying the causative agent, developing a vaccine and scaling up production to meet the requirements of the next pandemic is going to be almost impossible in the short time available. Increases in air travel since 1957 make this harder still. As a result, over 40 governments have taken the view that stockpiling antiviral drugs such as Roche's Tamiflu provide the best short-term option.

Despite these difficulties, vaccination remains the most effective way to prevent the spread of pandemic flu. Given the current pre-pandemic market demand, over 20 companies are developing vaccines against pandemic influenza. Many of these will be developing products based on H5N1 strains.

Three firms have turned to DNA vaccines, one of a number of alternative vaccine technologies currently being tested, to try to meet the demand, namely Merck & Co, Vical and PowderMed. Of the three firms, PowderMed has beaten DNA vaccine leader Vical to be the first with an influenza product to reach phase I clinical testing.

DNA vaccines are gaining popularity due to slowly accumulating efficacy data, the induction of broad-spectrum immunity, rapid production cycles and favorable stockpiling logistics. While these features are better matched with a pandemic, the technology is still experimental.

PowderMed development

DNA vaccines are based on plasmids constructed from the DNA that encodes the viral antigens. The DNA contained in the vaccine is produced using a well characterized E. coli fermentation process. During inoculation, the plasmid is taken up by cells at the site of injection (e.g. dendritic cells in the skin or muscle), where the gene encoding the viral antigen is transcribed. Fragments of the expressed protein are degraded into peptides, presented by both MHC class I and MHC class II molecules, thereby inducing both antibody and cellular responses.

In December 2005, PowderMed presented data from an earlier phase I trial conducted in 36 healthy volunteers. In this proof of concept study, a DNA influenza vaccine containing the hemagglutinin H3 gene from influenza A/Panama/2007/99 was able to induce the appropriate immune response to H3/panama. Importantly, the vaccine was shown to have a favorable effect on three genetically drifted H3 strains of influenza, suggesting a possible future use against emerging strains of influenza.

PowderMed's recently announced phase I trial is based on hemagglutinin H5, from influenza strain A/Vietnam/1194/2004. This H5 strain is more closely related to the virus that might cause the next pandemic.

PowderMed is betting that this vaccine will be effective against a future human pandemic virus derived from current avian H5N1. However, until the pandemic hits, we do not know for certain which form the virus will take and whether existing treatments will be effective.

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