Vical, with initial NIH funding, is pursuing a DNA-based vaccine in which genes encoding multiple influenza proteins are put into plasmids and injected, with the goal of evoking a complete response.
The issue, explains Samant, is that the H5N1 strain has a glycoprotein on the outside that evokes a humoral response. All the H5N1 vaccines under development (by the major vaccine manufacturers) evoke only antibody-mediated responses against this glycoprotein. But you need a T-cell response against the internal proteins to evoke a more complete response.
Samant says the DNA-based vaccinestill in preclinical stageshas elicited both antibody and T-cell immune response in mice. Further development depends on the availability of additional funding, he adds.
Vicals approach is relatively independent of the particular strain of flu because it attacks the internal proteins, which are well-conserved. As such, they will mutate less often than other characteristics of the virus.
With our method, it takes about six to eight weeks to make a construct, and then additional time to move it into production, Samant says, depending on the quantities needed and the availability of fermentation and purification capacity.
Whatever vaccine emerges, Theres not enough for all who may need it, Dr. Fauci says. Two to three billion doses will be needed worldwide, yet the world makes about 300 million doses of flu vaccine annually, Samant adds. As with last seasons flu vaccine, it will be allocated to high priority individualsprobably health care workers and the ill. Discussions to broaden the recommended group are ongoing.
Iomai (www.iomai.com) seems to have a solution to that challenge, and received a $2.9 million grant from the NIH to address that problem. Its immunostimulant (IS) patch not only improves the immune response rates but also enables a fraction of the normal dosage to confer the same immune response as the full dose delivered without the immunostimulant.
Our target is to use less than 1/20th of the normal flu dose, Dr. Glenn says. Then, whatever vaccine you have can be dramatically extended.
The company is testing two variations of the product for pandemic flu. In one, the vaccine is injected normally and an IS patch is applied over the injection site. In the other, the vaccine and immunostimulant are administered together through the patch.
The skin has a high level of exposure to a hostile microbial world, and so has a very high level of competent immune system components, explains Gregory M. Glenn, M.D., senior vp and CSO.
Unlike the contents of nicotine patches, which have to penetrate the skin, vaccines or immunostimulants must only reach the epidermis. Iomais IS patch uses the adjuvant heat-labile enterotoxin from E. coli to stimulate the Langerhans cells to take up the antigen and deliver it to the draining lymph nodes, which produce an immune response in the form of white blood cells.
In Phase II tests with individuals older than 60 years, placing the IS patch over or near the vaccine injection site resulted in seroconversion rates that were between 12 and 23% higher (depending on flu strain) than for a similar patient group that did not received the IS patch, and comparable to the results for healthy adults who did not receive the patch.
Other firms are concentrating on therapies, knowing that vaccines for pandemics would probably be in short supply.
Oseltamivir, called Tamiflu by Hoffman-La Roche (www. rocheusa. com), is, at this time, the only antiviral shown to be effective against the H5N1 (and H9N1 strains of) avian influenza virus in Asia, according to Julie L. Gerberding, J.D., director, Centers for Disease Control and Prevention, in testimony May 26 before the Subcommittee on Health of the Committee on Energy and Commerce, U.S. House of Representatives.
The company had practical experience with its use during an outbreak of the H7N7 strain of avian flu in the Netherlands in 2003, and has data from animal and in vitro studies, according to George B. Abercrombie, president and CEO, in testimony June 30 before the Committee on Government Reform, U.S. House of Representatives. The Strategic National Stockpile is holding enough to treat 2.26 million adults and 100,000 children.
Abercrombie calls for stockpiling Tamiflu before a pandemic occurs, in accordance with plans being developed by the HHS and WHO. The manufacturing process, he notes, takes 8 to 12 months, making surge capacity impossible.
To help ensure adequate supplies for stockpiling, Roche is doubling production capacity for this flu season and has enhanced its supply chain to yield an almost eight-fold increase in production capacity over 2003 levels. It also developed synthetic ingredients, which relieve pressure on natural resources.