Influenza Vaccine
Influenza remains a leading cause of illness and death around the world, causing an estimated $1 billion in direct
economic costs, as much as $15 billion in lost earnings due to illness, and 40,000 deaths annually in the U.S. alone.
In the last few years, new strains of avian influenza in Asia have caused mortality rates as high as 70% in the several
dozen humans who have contracted the disease. This has raised the specter that a new, potentially devastating human influenza
pandemic could occur sooner rather than later. Couple that with widely publicized vaccine shortages during the last two annual
outbreaks and it's easy to understand why an improved influenza vaccine has become one of the top priorities for U.S. public
health agencies and the NIH.
In October of 2007, AlphaVax concluded a phase 1 placebo-controlled, randomized, double-blind trial in
216 healthy adults, which evaluated the safety and humoral and cellular immune responses after one or two
inoculations. The replicon vector expressed the hemagglutinin (HA) gene derived from the A/Wyoming (H3N2)
strain of influenza virus. The vaccine was administered either subcutaneously or intramuscularly at two
dosage levels, and was found to be safe and well tolerated irrespective of the route or the dose given.
Both antibody and T cell responses were efficiently stimulated and persisted for the duration of the
four-month study. Among volunteers with prevaccination influenza antibody titers (measured by
hemagglutination inhibition, or “HI”) that were below levels thought to be protective, 77% and 80% of
these individuals receiving a single low or high dose, respectively, responded with protective HI antibody
titers. A second immunization in these individuals increased seroprotective responses to 86% for both dosage
levels. A rapid and dose-dependent T cell response (defined in antigen-specific IFN-gamma ELISPOT assays)
was also observed and remained significantly elevated for at least four months. A second immunization
extended the duration, but not the magnitude of these T cell responses. Comparable T cell responses are
typically not seen in adult populations with existing licensed influenza vaccines. HI antibody responses
are known to correlate with protection against influenza infection and reduction of clinical disease, and
influenza specific T cell responses are believed to function in eventual clearance of the virus from infected
individuals.
Additional government funding to improve public health preparedness for an influenza pandemic may create additional opportunities to leverage
our influenza program.