VaxInnate is developing an H1N1 flagellin-based vaccine for swine flu. The flagellin stimulates the immune cells in the body to release cytokine and immune-mediator molecules that initiate an immune response, notes David Taylor, M.D., chief medical officer.
VaxInnate uses HA and M2 proteins to stimulate an immune response to influenza virus. HA mutates rapidly, but the M2ectodomain (M2e) has remained virtually unchanged during the past century and across influenza A strains. “The body doesn’t recognize this as immunogenic,” Dr. Taylor says, until it is fused to flagellin.
To induce an immune response, VaxInnate fuses four copies of M2e to flagellin. “Unfortunately, this is the first M2e vaccine and we don’t know how protective it is in humans,” he says. Therefore, the company is determining its protective properties for influenza A. Pre-trials were expected to begin this spring, with a larger, 2,400 patient controlled trial scheduled to start in the autumn.
M2e and HA each can be produced in bacterial expression systems, shortening development time. Dosage, Dr. Taylor says, is one-tenth that required from egg-based vaccines, so “we can make tens of thousands of doses per liter of bacteria.” And, for a seasonal vaccine, he suggests VaxInnate can include four viral strains rather than the usual three.
NanoBio’s NanoStat™ vaccine platform mixes an antigen from an influenza strain with a proprietary nanoemulsion, according to David Peralta, vp, COO, and CFO. When administered in the nose, Mary R. Flack M.D., vp of clinical research explains, the vaccine “coats the mucosa” and then is taken up by dendritic cells that deliver the antigen to the lymph nodes, thymus, and spleen, triggering an immune response.
“The dendritic cells are specific for wanting to engulf lipids, so they take up the nanoemulsion-antigen mixture more efficiently than other vaccines,” says Dr. Flack.
In one day, 100 million doses of the emulsion can be made, claims Dr. Flack. “It’s very stable,” Peralta says, and has remained viable for more than three years. Once the nanoemulsion is made, it can be stored so different antigens can be mixed into the nanoemulsion as needed, making it easier to respond to emerging needs.
Phase I clinical trials of the nasal vaccine, NB–1008, are under way. In animal studies, it triggered a robust mucosal, systemic, and cellular immunity without inflammation or safety concerns. In ferrets, the responses were triggered with only 2% of the standard dosage. There are indications that cross protection may ensue.
The vaccine also is being investigated for hepatitis B, Haemophilus influenzae type B, RSV, cancer, anthrax, smallpox, and other diseases. Using the same technology platform, NanoBio is also developing a nasal spray that kills on contact any strain of influenza by attacking the lipid envelope that surrounds the virus, says Dr. Flack.