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H5N1 vaccine could be basis for life-saving stockpile
June 19, 2006St. Jude vaccine offers cross-protection in ferrets against different variants of H5N1, suggesting it could be stockpiled for use in the event of a human outbreak
Scientists at St. Jude Children's Research Hospital have announced that a vaccine they developed a few years ago against one antigenic variant of the avian influenza virus H5N1 may protect humans against future variants of the virus. Vaccines based on this model might therefore be suitable for stockpiling for use during a pandemic (worldwide epidemic) until a new vaccine could be developed specifically against the variant causing the outbreak, the researchers said. An antigen is a molecule that stimulates production of antibodies by the immune system.
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 naÃ-ve individuals will be the use of two doses, which in the ferrets triggered more antibody protection than a single dose. Immunologically naÃ-ve 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
St. Jude Children's Research Hospital
"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 naÃ-ve individuals will be the use of two doses, which in the ferrets triggered more antibody protection than a single dose. Immunologically naÃ-ve 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
St. Jude Children's Research Hospital
New vaccine may give long-term defense against deadly bird flu and its variant forms
A new vaccine under development may provide protection against highly pathogenic bird flu and its evolving forms, according to researchers at Purdue University and the Centers for Disease Control and Prevention who discovered the new preventative drug and have tested it in mice.
Live H5N1 avian flu virus vaccines show protection in animal studies
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.
Experimental vaccine protects lab animals against several strains of H5N1
Nations are preparing to stockpile vaccines against H5N1, the strain of influenza virus that experts fear could cause the next flu pandemic. But will these vaccines remain effective as the virus mutates?
Duke To Test Bird Flu Vaccine Dosing
A clinical trial to test different strengths of a vaccine designed to fight avian influenza will begin this month at Duke University Medical Center.
Bird-flu vaccine works at high doses; Focus turns to ways to stretch vaccine supply
An experimental vaccine against bird flu is safe and spurs the immune response considered necessary to protect against the deadly illness, at a dose several times larger than the traditional flu shot and in slightly more than half of people who received the largest dose.
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