Avian Flu Virus Vaccines Show Protection in Animal Studies

NIH's National Institute of Allergy and Infectious Disease.

Experimental vaccines based on live, weakened versions of H5N1 avian influenza viruses protected mice and ferrets from a deadly infection with naturally-occurring H5N1 flu viruses. The findings demonstrate that a vaccine based on one strain of the H5N1 flu virus could potentially protect against different emerging strains.

According to the World Health Organization, as of September 8, 2006, there have been 244 confirmed human cases of H5N1 infection, more than half of which were fatal. Public health officials worry that the H5N1 virus will evolve so that it can easily pass from person to person. Because humans have no pre-existing immunity to the H5N1 viruses, such a strain could spark an influenza pandemic.

In a study done under a cooperative research and development agreement between NIH's National Institute of Allergy and Infectious Diseases (NIAID) and MedImmune Inc, Dr. Kanta Subbarao and Dr. Brian Murphy, both from NIAID's Laboratory of Infectious Diseases, created three vaccines by combining modified proteins derived from virulent H5N1 flu viruses with proteins from an artificially weakened (attenuated) flu strain. The virulent H5N1 viruses were isolated from human cases in Hong Kong in 1997 and 2003, and Vietnam in 2004. The attenuated flu vaccine strain, which also serves as the basis for MedImmune's FluMist® influenza vaccine, was lab-grown in progressively colder temperatures ("cold-adapted") to prevent the resulting vaccine viruses from spreading beyond the relatively cool upper respiratory tract.

The results appeared in the September 12 issue of PLoS Medicine. Mice given a single dose of the vaccines via nose drops survived infection with H5N1 viruses found circulating in Asia between 1997 and 2005. Further, mice that received a second dose of vaccine 28 days after the initial inoculation demonstrated a stronger and more rapid immune response and almost complete protection from respiratory infection when exposed to the naturally occurring H5N1 viruses. Ferrets exhibited similar results when given two doses of the vaccine viruses.

"It is impossible to predict how the H5N1 virus will evolve or which strain, if any, will cause an influenza pandemic," Dr. Subbarao said. "To be prepared, we need to select a vaccine capable of inducing an effective human immune response against a range of H5N1 viruses that may emerge in the future. This study shows that such cross-protection can be achieved in small animals."

NIAID and MedImmune launched a phase 1 trial in June to begin evaluating a live, attenuated H5N1 virus vaccine in humans.