A prepublication report on the study appears in the online issue of Journal of Infectious Diseases (JID).
The researchers showed that the vaccine completely protected ferrets from a lethal nasal infection against not only the original virus the vaccine was made to thwart, but also against a newer variant that has already proved fatal to humans. The ferrets experienced a more significant reduction of virus multiplication than otherwise would have occurred, the researchers reported. Moreover, the infections failed to spread out of the upper respiratory tract to the lungs or brain.
"These findings are especially significant because ferrets are known to be an excellent and accurate model of influenza infection and immune response in humans," said Elena Govorkova, Ph.D., a staff scientist in the Department of Infectious Diseases at St. Jude. "Restricting the infection to the upper respiratory tract is important since in humans the virus has been isolated from specimens taken from the cerebrospinal fluid, feces, throat and blood serum. Therefore, limiting the spread of virus in an infected human is crucial to saving that person's life." Govorkova is the lead author of the JID paper and led the research team conducting the study.
The team also showed that the optimal strategy for vaccination of immunologically naïve individuals will be the use of two doses, which in the ferrets triggered more antibody protection than a single dose. Immunologically naïve individuals are those whose immune systems have not been stimulated to respond to a particular antigen.
The St. Jude study was the first one to show cross-reactive immunity against current H5N1 variants in ferrets, according to Robert Webster, Ph.D., a member of the Infectious Diseases department and holder of the Rose Marie Thomas Chair at St. Jude. Webster is an internationally renowned expert on avian influenza viruses and is senior author of the report in JID.
Cross-reactive immunity is the protection that a virus vaccine confers against not only the same virus, but also against variants of the original virus. "Such cross-protection would allow the use of a stockpiled vaccine until a vaccine against the specific variant causing the outbreak is developed," Webster said. "So our success with ferrets is extremely promising news."
Using reverse genetics, the team mixed genes from a safe, laboratory bird flu virus with a gene for the hemagglutinin (HA) protein from the H5N1 virus isolated in Hong Kong. The virus uses the HA proteins on its surface to infect cells in the respiratory tract. The resulting vaccine had the outside appearance of a dangerous virus that would stimulate the immune system, but the inside genes of a harmless variety of virus that could not cause disease. The St. Jude team was the first to use reverse genetics to make a vaccine against H5N1 that moved out of the laboratory and into clinical trials: http://www.stjude.org/media/0,2561,453_5484_4638,00.html.
Other authors of the study include Richard Webby, Jennifer Humberd and Jon Seiler, all of St. Jude.
This work was supported in part by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health and ALSAC.
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fund-raising organization. For more information, please visit www.stjude.org.
Journal
The Journal of Infectious Diseases