SARS Vaccine Linked To Liver Damage In Ferret Study
"The team next tested whether the antibodies would attack spike proteins from two SARS strains isolated from civets, from which the virus is thought to have originally jumped into humans. In this case, they found hints that the antibodies actually boosted the ability of the virus to infect cells...
...The results show that the virus changes over time, so that a strain that crops up in one outbreak might be quite different from that in a later outbreak. "This virus is not standing still and we need to take this into account," Nabel says...
...This raises the prospect that a vaccine against one strain of SARS virus could prove ineffective against others. Worse, a jab against one strain might even aggravate an infection with SARS virus from civets or another species. "It's obviously a concern," Nabel says.....
...This virus is not standing still. We need to take this into account....
This would not be the first case where exposure to one strain of a virus can worsen infection with another. In the mosquito-borne disease dengue fever, for example, people who have been infected with one strain are likely to suffer a worse infection if they pick up a second strain.
Ferrets vaccinated with rMVA-S and exposed to SARS-CoV had elevated levels of an enzyme that indicates liver damage.
"Extra caution should be taken in proposed human trials of SARS vaccines due to the potential liver damage from immunization and virus infection," the research report states.
Imagine putting your confidence in these so called experts. This and so many other medical practices continue to open up one Pandora's box after another, yet once approved, then for some strange reason, no new evidence of harm seems to be sufficient...
They are always demanding proof of damages but can never provide us with proof for safety thus condemning the their constituents to ongoing harm. What abuse of science?Far safer treatments such as those discussed in "SARS - Pneumonia-like respiratory disease another gravy train..." are totally neglected regardless of efficacy as profits and funding come first at the expense of our health and real science.
Chris Gupta
------------------Nature, UK
10 January 2005; | doi:10.1038/news050110-3
Caution raised over SARS vaccine
Helen Pearson
Jab against one strain might worsen infection with others.
A cautionary note has been sounded for those developing vaccines against severe acute respiratory syndrome (SARS). Some vaccines could prove useless against certain strains, or even worsen the infection, a preliminary study suggests.
SARS killed nearly 800 people when it emerged from China in 2002 and spread around the world in the first half of 2003. Only a handful of isolated outbreaks have been spotted since that initial epidemic.
Aware that the disease could re-emerge, several groups have been trying to make a vaccine against the virus. They are mainly trying to find ways to expose people to a protein on the virus's coat, called the spike protein, which helps it to enter cells. This should jolt the immune system into recognizing the virus during a future infection and making antibodies that attack it.
In the new study, Gary Nabel of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, and his co-workers injected mice with spike protein from a SARS virus taken from a human patient infected in early 2003. They then collected the antibodies the animals produced.
In lab experiments, they showed that these antibodies were unable to attack spike protein from a different strain of SARS, isolated from a patient infected in late 2003.
The team next tested whether the antibodies would attack spike proteins from two SARS strains isolated from civets, from which the virus is thought to have originally jumped into humans. In this case, they found hints that the antibodies actually boosted the ability of the virus to infect cells. The study is published in the Proceedings of the National Academy of Science1.
Quick change
The results show that the virus changes over time, so that a strain that crops up in one outbreak might be quite different from that in a later outbreak. "This virus is not standing still and we need to take this into account," Nabel says.
This raises the prospect that a vaccine against one strain of SARS virus could prove ineffective against others. Worse, a jab against one strain might even aggravate an infection with SARS virus from civets or another species. "It's obviously a concern," Nabel says.
This virus is not standing still. We need to take this into account.
Gary Nabel National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.
The experiments are still preliminary: there is no sign from those testing vaccines in animals that they actually worsen an infection. But Nabel cautions that researchers should watch carefully for signs this is happening.
He adds that some pilot vaccines, such as one he is testing in a small human clinical trial, could get around the problem because they also provoke other parts of the immune system to cripple the virus.
Find the mechanismThis would not be the first case where exposure to one strain of a virus can worsen infection with another. In the mosquito-borne disease dengue fever, for example, people who have been infected with one strain are likely to suffer a worse infection if they pick up a second strain.
In the case of SARS, it remains unclear how antibodies might be helping some viral strains into cells. "It's an interesting phenomenon," says Chris Olsen who studies animal viruses related to SARS at the University of Wisconsin-Madison. Figuring this out might thwart potential problems in vaccines, he says.
Yang, Z-Y. et al. Proc. Natl Acad. Sci. USA published online
doi:10.1073/pnas.0409065102 2005.
http://www.pnas.org/cgi/doi/10.1073/pnas.0409065102
SARS vaccine linked to liver damage in ferret studyCIDRAP
Amy L. Becker Staff Writer
Dec 6, 2004 (CIDRAP News) - Researchers in Canada who found hepatitis in ferrets after injecting the animals with an experimental vaccine for SARS (severe acute respiratory syndrome) are urging caution as other investigators develop and test SARS vaccines.
As reported in the November issue of the Journal of Virology, the study involved a vaccine developed by senior author Jingxin Cao, PhD, of the Public Health Agency of Canada's National Microbiological Laboratory in Winnipeg, Man. Cao had created a vaccine from recombinant modified vaccinia virus Ankara (rMVA) and the distinctive spike protein that marks the SARS coronavirus (SARS-CoV). The trial vaccine is called rMVA-S.
The team chose ferrets for the study on the basis of their reported susceptibility to SARS infection, Cao told CIDRAP News.
At the Canadian Science Centre for Human and Animal Health's Biosafety Level 4 lab in Winnipeg, three ferrets were injected with the rMVA-S vaccine, three with parental MVA, and three with saline solution. They received booster immunizations 2 weeks later.
Then the ferrets were exposed intranasally to the SARS virus, which infected more than 8,000 people and killed 774 between November 2002 and July 2003.
On the plus side, immunization with rMVA-S induced a rapid immune response following exposure to the virus, the researchers wrote. The ferrets displayed no clinical signs of illness, but viral RNA was found in pharyngeal swabs and blood samples taken from all the ferrets.
But researchers unexpectedly discovered a downside when they checked the ferrets' liver health. Ferrets vaccinated with rMVA-S and exposed to SARS-CoV had elevated levels of an enzyme that indicates liver damage. Examination of liver sections showed that the ferrets had severe hepatitis. Only mild hepatitis was found in the ferrets injected with parental MVA or saline.
It's uncommon to perform the tests that revealed the hepatitis, said Kelly Keith, acting communications manager for the Canadian Science Centre for Human and Animal Health. This study will help ensure that any other SARS vaccine will be safer, as scientists should know to check for this possible side effect.
"Extra caution should be taken in proposed human trials of SARS vaccines due to the potential liver damage from immunization and virus infection," the research report states.
Cao said he hopes that others recognize the significance of the hepatitis among the vaccinated ferrets. "For future human vaccine development, we must pay attention to that effect," he said.
The lead author of the study, Hana Weingartl, PhD, head of special pathogens for Canada's National Microbiology Laboratory in Winnipeg, said she and her fellow researchers are seeking a grant to continue their work. "We would like to look more closely at why we saw the liver damage in those animals," she said. "It would be good to know what not to do."
The findings underscore how little is understood about SARS, which emerged in southern China in November 2002. Since its discovery, scientists have raced to contain it and develop a vaccine. Weingartl and Cao's study is one of several vaccine investigations in various stages in several countries.
Researchers need a better understanding of how the virus damages the host, Weingartl said.
In an unrelated SARS vaccine investigation, the Chinese government yesterday announced that a vaccine proved safe and effective in a phase 1 clinical trial. Thirty-six volunteers who had been vaccinated reported no unusual physical reactions after 56 days, Agence France-Presse reported (AFP). In addition, antibodies were found in 24 of those vaccinated, the story said.
Testing began in May with 18 men and 18 women from 21 to 40 years old following what the government termed successful animal tests, AFP reported. The vaccine won't be ready for commercial use until two more testing phases are completed.
Weingartl H, Czub M, Czub S, et al. Immunization with modified vaccinia virus Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets. J Virology 2004;78(22):12672-6 [Abstract]
posted by Chris Gupta on Friday January 14 2005
updated on Saturday September 24 2005URL of this article:
http://www.newmediaexplorer.org/chris/2005/01/14/sars_vaccine_linked_to_liver_damage_in_ferret_study.htm
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