13 September 2006
Live H5N1 Avian Flu Virus Vaccines Protect Animals from Infection, September 13, 2006(Vaccine for one H5N1 strain potentially could protect against emerging strains)
Washington -- Experimental vaccines based on live, weakened versions of different strains of the H5N1 avian influenza virus were tested in mice and ferrets and protected the animals from a deadly infection from naturally occurring H5N1 flu viruses.
The findings -- from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH) -- also are encouraging, the researchers say, because they demonstrate the ability to create a vaccine based on one particular strain of the H5N1 flu virus that potentially could protect against different emerging H5N1 flu strains.
Leading the research were senior investigator Dr. Kanta Subbarao and co-chief Dr. Brian Murphy of NIAID’s Laboratory of Infectious Diseases.
The study was the result of an agreement between NIAID and Maryland biotechnology company MedImmune.
“This is an excellent example of the NIH and industry working together to find scientific solutions to potential public health problems,” said NIH Director Dr. Elias Zerhouni. “Developing a vaccine that could protect against a potential influenza pandemic is a top priority for all of us.”
PREPARING FOR PANDEMIC
As of September, 244 human cases of H5N1 infection have been confirmed worldwide, more than half fatal, according to the World Health Organization.
Public health officials worry that the H5N1 virus will evolve to become easily transmissible among people, potentially sparking an influenza pandemic because people have no immunity to the H5N1 viruses.
“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 Dr. Anthony Fauci.
Study findings, “suggest that vaccines based on live but weakened versions of the H5N1 avian influenza virus may quickly stimulate protective immunity,” he added. “We are further exploring this live, attenuated [weakened] vaccine strategy as one of several tools we hope to have available in the event of an influenza pandemic.”
THE STUDY
The NIAID and MedImmune research team created three vaccines by combining proteins from an artificially weakened flu strain with modified proteins derived from virulent H5N1 flu viruses.
The virulent H5N1 viruses were isolated from human cases that occurred in Hong Kong in 1997 and 2003, and in Vietnam in 2004.
The weakened flu vaccine strain, also the basis for MedImmune’s FluMist® flu vaccine – a nasal spray flu vaccine licensed in 2003 – was lab-grown in progressively colder temperatures (“cold-adapted”) to prevent the resulting vaccine viruses from spreading and causing disease beyond the relatively cool upper-respiratory tract.
Large quantities of the resulting cold-adapted viruses were grown in chicken eggs, and the safety of the vaccine viruses was evaluated in chickens and mice.
The wild-type H5N1 viruses have been shown to replicate in animal lungs and brains. So as another safety measure the researchers tested the ability of the 1997 and 2004 strains of the vaccine viruses to replicate in mice and ferrets.
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.
To evaluate the protective ability of the vaccines, the researchers gave the mice a single dose of vaccine virus via nose drops. All the mice survived infection with the 1997 and 2004 H5N1 wild-type viruses, including two more recent strains of the H5N1 virus found circulating in Vietnam and Indonesia in 2005.
The mice that received a second dose of vaccine 28 days after the initial inoculation had a stronger and faster immune response and almost complete protection from respiratory infection when exposed to the naturally occurring H5N1 viruses. Ferrets showed similar results when given two doses of the vaccine viruses.
SAFETY AND IMMUNE RESPONSE
“It is impossible to predict how the H5N1 virus will evolve or which strain, if any, will cause an influenza pandemic,” said Subbarao. “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 showed such “cross-protection” in small animals.
“The next step,” he said, “is to evaluate in people the safety and immune response induced by these vaccines to see if they produce cross-reactive antibodies that are likely to protect against different H5N1 viruses.”
In June, NIAID and MedImmune launched a study to evaluate the safety and immunogenicity – the capacity to induce an immune response – of a live, attenuated H5N1 vaccine based on the 2004 H5N1 virus strain.
The study, being performed in an isolation unit at Johns Hopkins Bloomberg School of Public Health Center for Immunization Research in Maryland, is evaluating the vaccine’s safety and immunogenicity in 20 healthy people between ages 18 and 49. Results from that study are not yet available.
The full text of the press release is available at the NIH Web site.
Additional information about flu vaccines is available online.
For ongoing coverage of avian influenza and efforts to combat it, see Bird Flu.
