When tested in mice and ferrets, experimental vaccines based on live, weakened versions of different strains of the H5N1 avian influenza virus were well-tolerated and protected the animals from a deadly infection with naturally occurring H5N1 flu viruses.
The findings, which appear in the September 12 issue of PLoS Medicine, are also encouraging, the researchers say, because they demonstrate the ability to create a vaccine based on one particular strain of the H5N1 flu virus that could potentially protect against different emerging H5N1 flu strains.
Senior investigator Kanta Subbarao, M.D., M.P.H., and co-chief Brian Murphy, M.D., both of the Laboratory of Infectious Diseases at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), led the research. The study was the result of a cooperative research and development agreement between NIAID and MedImmune Inc., of Gaithersburg, Md.
"This is an excellent example of the NIH and industry working together to find scientific solutions to potential public health problems," notes NIH Director Elias A. Zerhouni, M.D. "Developing a vaccine that could protect against a potential influenza pandemic is a top priority for all of us."
"If an influenza pandemic were imminent or under way, we would need a vaccine that could stimulate immunity quickly, preferably with a single dose," says NIAID Director Anthony S. Fauci., M.D. "The encouraging findings of this study suggest that vaccines based on live but weakened versions of the H5N1 avian influenza virus may quickly stimulate protective immunity. We are further exploring this live, attenuated vaccine strategy as one of several tools that we hope to have available in the event of an influenza pandemic."
As of September 8, 2006, there have been 244 confirmed human cases of H5N1 infection and more than half of those were fatal, according to the World Health Organization (WHO). Public health officials worry that the H5N1 virus will evolve to become easily transmissible among people, potentially sparking an influenza pandemic, because humans have no pre-existing immunity to the H5N1 viruses.
The NIAID and MedImmune research team 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. Large quantities of the resulting cold-adapted viruses were grown in chicken eggs.
The safety of the vaccine viruses was evaluated in chickens and mice. In chickens, the H5N1 vaccine viruses were not lethal, while each of the three strains of the "wild-type" (naturally occurring) H5N1 viruses were. Similarly, the vaccine viruses were not lethal in mice, but the 1997 and 2004 strains of the wild-type H5N1 viruses were. The 2003 strain of the H5N1 wild-type virus was not tested in mice because the researchers found that the virus was lethal in those animals only at very high doses. Because the wild-type H5N1 viruses have been shown to replicate in animal lungs and brains, the researchers tested the ability of the 1997 and 2004 strains of the vaccine viruses to replicate in mice and ferrets as an additional safety measure In mice, the vaccine viruses replicated in the respiratory tract but did not spread to the animals’ brains. In ferrets, the H5N1 vaccine viruses did not replicate in the lungs or the brain.