The most recent avian influenza concerns first arose in 1997, when the H5N1 avian influenza virus first moved into humans. The current outbreak of H5N1 avian influenza in Southeast Asia has resulted in more than 100 human cases, in Cambodia, China, Indonesia, Thailand and Vietnam, with a mortality rate of approximately 50 percent. Despite the death or destruction of an estimated 150 million birds, the virus is now considered endemic in a number of regions in Southeast Asia.

In 1999, two years after the first concerns over H5N1, another novel avian flu virus, H9N2, caused illness in Hong Kong. It reappeared in 2003. H5N1, H9N2 and other avian flu viruses are of ongoing concern to global public health officials, who are closely monitoring their continued presence in birds, patterns of infections in humans, and abilities to change and become more transmissible among people.

Novartis' Leading Avian Influenza Studies

Novartis started working on avian flu soon after the H5N1 outbreak in Hong Kong first affected humans in 1997. The deadliness of the H5N1 virus among birds that made it such a concern also made it problematic to use in vaccine development—the virus tended to kill the chicken eggs that served as the first step of the vaccine production process. Novartis instead worked with a less pathogenic strain of H5 and consequently developed an H5N3 virus vaccine for testing against the H5N1 virus strain.

Studies of this vaccine included Novartis' adjuvant, MF59. An adjuvant is a substance that is added to a vaccine to enhance the body’s immune response to the vaccine’s active constituent, called the antigen. The studies found that, without the adjuvant, a range of doses of vaccine did not induce protection. With the adjuvant, however, the vaccine induced protective antibody levels against the original H5N1 strain, including when used at low doses (7.5 micrograms). Furthermore, people immunized with the adjuvanted vaccine in this trial showed protective antibody titers not just against the original H5N1 strain, but also against drifted strains of H5N1 that had changed over time.

These studies concluded that the use of Novartis’' adjuvant MF59 in an avian flu vaccine may:

• Allow dose-sparing, where using less vaccine per person would allow more people to be immunized, and
• Offer cross-protection, where the vaccine may offer protection against an avian flu virus even as it changed over time

The studies are reported in Lancet 2001; 357:1937-43; Vaccine 2003; 21:1987-93; and The Journal of Infectious Diseases 2005; 191:1210-5.

Government Studies

In 2004, Novartis won contracts from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH) under HHS, to provide H5N1 and H9N2 influenza vaccine candidates for NIAID-sponsored studies.

In October 2005, Novartis reported promising data from an H9N2 study. Similar to Novartis’' previous work, the study found that all vaccine formulations containing MF59 were highly immunogenic, even at the lowest dose of 3.75 micrograms, which represents a quarter of the dose used per strain in seasonal flu vaccines. NIAID director Anthony S. Fauci, M.D., called the study data “very encouraging” and, when asked about similar expectations for the upcoming H5N1 trial, stated, “There's no reason to believe the results will be any different.” An H5N1 influenza vaccine trail with Novartis' vaccine will take place in early 2006. NIAID answered questions about the H5N1 virus vaccine trials in April 2005.

Avian Influenza Vaccine Stockpiles

Novartis will produce H5N1 avian influenza vaccine for a U.S. government stockpile, as announced in October 2005. Novartis has engaged in discussions with a number of governments around the world on a range of pandemic measures, including vaccine stockpiling and advance purchase contracts. As a leading influenza vaccine manufacturer, Novartis is pleased to bring the capabilities of its influenza production facilities to this global effort.

Flu Cell Culture

Cell culture-derived influenza vaccine technology (“flu cell culture”) is an innovative production process for the manufacturing of flu vaccine on the basis of cell cultures. Cell culture–derived influenza vaccines (commonly referred to as "flu cell culture" vaccines) use cell cultures rather than chicken eggs for antigen production. Current egg-derived vaccines production requires up to nine months, and this lead time can hinder the response to unanticipated demands such as the discovery of pandemic strains, production failures and seasonal influenza virus strain changes. In contrast, flu cell culture production enables flexible, faster start-up of vaccine manufacturing, providing a particularly important advantage in the event of an influenza pandemic. Novartis is a leader in cell culture-derived influenza vaccine development, with advances in its U.S. and EU trials announced in October 2005.