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Scientists Test Chimera Vaccine
by: Stephanie L. Church, News Editor
January 2006 Article # 6475
Article Tools
A new research model has been developed and successfully used to test a new type of vaccine against West Nile virus (WNV). Maureen Long, DVM, PhD, Dipl. ACVIM, assistant professor at the University of Florida, proved a chimera WNV vaccine was safe and effective using this new research model developed by Dick Bowen, DVM, PhD, of Colorado State University. Long presented her findings on Dec. 5, 2005, at the American Association of Equine Practitioners Convention.
Long says you only have to look as far as the U.S. human blood donor seroprevalence data for 2005 to see that WNV is still a present threat, so veterinarians and horse owners should continue to look for better ways to safeguard horses against the disease.
Scientists have been limited in testing WNV vaccines in recent years because until now, they were unable to consistently infect an unvaccinated (control) horse with WNV and cause consistent clinical signs.
"As a disease is around for awhile, we start getting into better technologies," Long said. "I think we need to look at these better technologies, get away from using adjuvants (substances that are added to vaccines to improve immune response so less vaccine is needed, but which can cause site reactions), and find solutions that may be more efficacious for a longer duration. Also, these (new vaccines) will have less over-the-counter capability, and put the vaccines, I hope, back into the hands of the practitioner."
A killed WNV vaccine for horses was introduced in 2001, and a modified-live recombinant virus vaccine was approved in 2003. Not much is known about how effective these vaccines are in preventing overt WNV disease in horses, noted Long.
"The chimera vaccine is basically two organisms that have been genetically spliced together," Long explained. Scientists essentially started with the backbone of a yellow fever vaccine that has prevented disease in 95% of more than 400 million people. Yellow fever was used because it is closely related to WNV. A WNV gene that is important in WNV immunity was placed into this vaccine.
Long performed vaccine safety trials in weanlings between four and six months of age that were kept in biosafety level (BSL) 2 and 3 laboratories, which are designed to prevent escape of dangerous viruses. She and colleagues determined that vaccinated horses could not develop infection or shed the vaccine virus and infect unvaccinated horses when they received overdoses of the chimera vaccine. Additionally, there were no physical or neurological abnormalities in these vaccinated horses.
Moving onto efficacy trials for the vaccine, the scientists had to work in stricter BSL3 conditions because they were working with live WNV. Twenty-eight days after intramuscular vaccination of the test group with the chimera vaccine, Long challenged the vaccinated horses and the unvaccinated controls using the new model, which involves direct inoculation of live WNV into the horses' cerebrospinal fluid (CSF).
The horses were watched at all times for signs of illness. In the study, "19 of 20 vaccinates (95%) met the criteria for satisfactory protection against WNV disease," Long said. One of the vaccinated horses showed mild ataxia (incoordination) and muscle twitching for two consecutive days post-WNV challenge.
In 10 unvaccinated control horses that received WNV, Long said virus could be detected in their blood two to five days after live challenge. All of the controls developed clinical signs of encephalomyelitis, including increased rectal temperature, anorexia, change in mental activity, weakness, paresis (partial paralysis), ataxia (incoordination), and muscle twitching seven to 10 days after challenge.
"Vaccinates developed a neutralizing antibody titer between seven and 10 days post-vaccination, which is pretty remarkable," she said because these horses received only one injection of vaccine.
Until the time of these studies, needle challenge and mosquitoes had been used to introduce WNV into horses. Only one in 11 of these horses actually develops clinical signs by these routes. Thus, the level of virus in the blood was the only parameter of that indicated that a horse had been test challenged.
Eight of the 10 nonvaccinated horses were euthanatized and necropsied before the end of the 28-day challenge period. Study investigators examined the tissues on the remaining horses in the study after 28 days. All of the nonvaccinated horses showed internal signs of WNV infection, but only two of the 20 vaccinates showed microscopic changes in their organs consistent with WNV infection. "In conclusion, this vaccine is safe and does not revert to virulence (disease-causing state)," Long said.
"This vaccine is efficacious in a single, non-adjuvanted dose. This is quite exciting when one has to keep giving booster injections (with current vaccines) and horses get sore and febrile (feverish).
"Based on my clinical experience, this model mimics clinical disease in that it causes viremia (presence of virus in the bloodstream), consistent clinical signs, and histopathology (tissue changes) that are consistent with West Nile virus encephalomyelitis," she added.
Editor's note: Intervet International (makers of the chimera vaccine based on technology of Acambis, Inc.), financially supported this study, but Long has no financial consultancy with the company. An Intervet consultant was a co-investigator in these studies.
What is a Chimera Vaccine?
Chimera yellow fever (YF) vaccines are created by weakening the virus' replication gene, which reduces its ability to replicate and cause disease. By replacing the structural genes of the weakened YF virus with those of West Nile virus, a new attenuated chimeric virus is created that will stimulate WNV immunity without causing disease. So, what's the difference between the WNV chimera vaccine (Intervet), the recombinant canarypox-vectored vaccine (Merial), and the DNA vaccine (Fort Dodge)? A chimera is a hybrid of two closely related microorganisms--it cannot replicate if the two are taken apart. A vectored vaccine relies on an organism (vector) that carries foreign genes to the horse, but that organism can replicate without the gene inserts. A DNA vaccine essentially contains naked DNA that replicates when it reaches certain cells in the horse.
by: Stephanie L. Church, News Editor
January 2006 Article # 6475
Article Tools
A new research model has been developed and successfully used to test a new type of vaccine against West Nile virus (WNV). Maureen Long, DVM, PhD, Dipl. ACVIM, assistant professor at the University of Florida, proved a chimera WNV vaccine was safe and effective using this new research model developed by Dick Bowen, DVM, PhD, of Colorado State University. Long presented her findings on Dec. 5, 2005, at the American Association of Equine Practitioners Convention.
Long says you only have to look as far as the U.S. human blood donor seroprevalence data for 2005 to see that WNV is still a present threat, so veterinarians and horse owners should continue to look for better ways to safeguard horses against the disease.
Scientists have been limited in testing WNV vaccines in recent years because until now, they were unable to consistently infect an unvaccinated (control) horse with WNV and cause consistent clinical signs.
"As a disease is around for awhile, we start getting into better technologies," Long said. "I think we need to look at these better technologies, get away from using adjuvants (substances that are added to vaccines to improve immune response so less vaccine is needed, but which can cause site reactions), and find solutions that may be more efficacious for a longer duration. Also, these (new vaccines) will have less over-the-counter capability, and put the vaccines, I hope, back into the hands of the practitioner."
A killed WNV vaccine for horses was introduced in 2001, and a modified-live recombinant virus vaccine was approved in 2003. Not much is known about how effective these vaccines are in preventing overt WNV disease in horses, noted Long.
"The chimera vaccine is basically two organisms that have been genetically spliced together," Long explained. Scientists essentially started with the backbone of a yellow fever vaccine that has prevented disease in 95% of more than 400 million people. Yellow fever was used because it is closely related to WNV. A WNV gene that is important in WNV immunity was placed into this vaccine.
Long performed vaccine safety trials in weanlings between four and six months of age that were kept in biosafety level (BSL) 2 and 3 laboratories, which are designed to prevent escape of dangerous viruses. She and colleagues determined that vaccinated horses could not develop infection or shed the vaccine virus and infect unvaccinated horses when they received overdoses of the chimera vaccine. Additionally, there were no physical or neurological abnormalities in these vaccinated horses.
Moving onto efficacy trials for the vaccine, the scientists had to work in stricter BSL3 conditions because they were working with live WNV. Twenty-eight days after intramuscular vaccination of the test group with the chimera vaccine, Long challenged the vaccinated horses and the unvaccinated controls using the new model, which involves direct inoculation of live WNV into the horses' cerebrospinal fluid (CSF).
The horses were watched at all times for signs of illness. In the study, "19 of 20 vaccinates (95%) met the criteria for satisfactory protection against WNV disease," Long said. One of the vaccinated horses showed mild ataxia (incoordination) and muscle twitching for two consecutive days post-WNV challenge.
In 10 unvaccinated control horses that received WNV, Long said virus could be detected in their blood two to five days after live challenge. All of the controls developed clinical signs of encephalomyelitis, including increased rectal temperature, anorexia, change in mental activity, weakness, paresis (partial paralysis), ataxia (incoordination), and muscle twitching seven to 10 days after challenge.
"Vaccinates developed a neutralizing antibody titer between seven and 10 days post-vaccination, which is pretty remarkable," she said because these horses received only one injection of vaccine.
Until the time of these studies, needle challenge and mosquitoes had been used to introduce WNV into horses. Only one in 11 of these horses actually develops clinical signs by these routes. Thus, the level of virus in the blood was the only parameter of that indicated that a horse had been test challenged.
Eight of the 10 nonvaccinated horses were euthanatized and necropsied before the end of the 28-day challenge period. Study investigators examined the tissues on the remaining horses in the study after 28 days. All of the nonvaccinated horses showed internal signs of WNV infection, but only two of the 20 vaccinates showed microscopic changes in their organs consistent with WNV infection. "In conclusion, this vaccine is safe and does not revert to virulence (disease-causing state)," Long said.
"This vaccine is efficacious in a single, non-adjuvanted dose. This is quite exciting when one has to keep giving booster injections (with current vaccines) and horses get sore and febrile (feverish).
"Based on my clinical experience, this model mimics clinical disease in that it causes viremia (presence of virus in the bloodstream), consistent clinical signs, and histopathology (tissue changes) that are consistent with West Nile virus encephalomyelitis," she added.
Editor's note: Intervet International (makers of the chimera vaccine based on technology of Acambis, Inc.), financially supported this study, but Long has no financial consultancy with the company. An Intervet consultant was a co-investigator in these studies.
What is a Chimera Vaccine?
Chimera yellow fever (YF) vaccines are created by weakening the virus' replication gene, which reduces its ability to replicate and cause disease. By replacing the structural genes of the weakened YF virus with those of West Nile virus, a new attenuated chimeric virus is created that will stimulate WNV immunity without causing disease. So, what's the difference between the WNV chimera vaccine (Intervet), the recombinant canarypox-vectored vaccine (Merial), and the DNA vaccine (Fort Dodge)? A chimera is a hybrid of two closely related microorganisms--it cannot replicate if the two are taken apart. A vectored vaccine relies on an organism (vector) that carries foreign genes to the horse, but that organism can replicate without the gene inserts. A DNA vaccine essentially contains naked DNA that replicates when it reaches certain cells in the horse.
