A newly identified inhibitor of the anthrax toxin may be used to develop a safer and more effective vaccine and act as a therapeutic agent after exposure say researchers from Massachusetts and Germany. Their findings appear in the June 2005 issue of the journal Infection and Immunity.
Anthrax is a highly contagious and toxic disease that results from infection with the bacterium Bacillus anthracis. If not caught immediately, those infected may die within a matter of days. Anthrax poses a deadly threat as a potential biological weapon placing added emphasis on the need for a safe and effective vaccine. The vaccine currently available doesn't protect against the bacilli and may be hazardous to its host when used immediately after exposure.
In the study researchers infected two groups of mice with anthrax and immunized one group with a dominant-negative inhibitor (DNI) and the other with a protective antigen (PA) currently used in the anthrax vaccine. They monitored the mice for several weeks and found that DNI alone produced higher immune responses than PA. Due to DNI's ability to inhibit the anthrax toxin, researchers also believe that DNI-based vaccines may increase immunity and provide therapeutic activity when administered postexposure.
"The strong immunogenicity and retained antigenicity of DNI suggest that DNI is a promising and potentially safer candidate for use in an anthrax vaccine than PA," say the researchers. "Moreover, in the event of anthrax infection, the administration of DNI can serve not only as an antitoxic therapy as an immediate response but also as a prophylactic vaccine to prevent late-onset or future anthrax infection."
(B.A. Aulinger, M.H. Roehrl, J.J. Mekalanos, R.J. Collier, J.Y. Wang. 2005. Combining anthrax vaccine and therapy: a dominant-negative inhibitor of anthrax toxin is also a potent and safe immunogen for vaccines. Infection and Immunity, 73. 6: 3408-3414.)
Old Drug May Offer New Hope in Treating SARS
Cinanserin, a drug that underwent preliminary clinical testing on humans in the 1960's, may inhibit the SARS virus say researchers from Europe and China. Their findings appear in the June 2005 issue of the Journal of Virology.
Severe acute respiratory syndrome (SARS) emerged as a highly infectious respiratory disease in 2002 and reached epidemic levels within six months. An estimated 8,096 cases were reported resulting in 774 deaths throughout 29 countries. Although the causative agent was quickly identified as a new strain of the coronavirus, an effective method of treatment has yet to be determined.
In the study researchers scanned a database of 8,000 existing drugs for those that would likely bind to the 3C-like proteinase of SARS. Cinanserin, a well-characterized serotonin antagonist, scored high in the screening and was selected for further experimentation. The antiviral activity of cinanserin was evaluated in tissue samples containing the SARS virus and revealed a strong inhibition of coronavirus replication at nontoxic drug concentrations.
"These findings demonstrate that the old drug cinanserin is an inhibitor of SARS-CoV replication, acting most likely via inhibition of the 3CL proteinase," say the researchers.
(L. Chen, C. Gui, X. Luo, Q. Yang, S. Gunther, E. Scandella, C. Drosten, D. Bai, X. He, B. Ludewig, J. Chen, H. Luo, Y. Yang, Y. Yang, J. Zou, V. Thiel, K. Chen, J. Shen, X. Shen, H. Jiang. 2005. Cinanserin is an inhibitor of the 3C-like proteinase of severe acute respiratory syndrome coronavirus and strongly reduces virus replication in vitro. Journal of Virology, 79. 11: 7095-7103.)
One Vaccine May Protect Against Both Parainfluenza and Influenza Viruses
Researchers from Wisconsin and Japan have developed a live vaccine that may protect against both the influenza and human parainfluenza viruses. They report their findings in the June 2005 issue of the Journal of Virology.
Influenza is responsible for 3 to 5 million cases of human respiratory disease each year, of which 250,000 to 500,000 are fatal. Approximately 16,300 to 96,500 patients are hospitalized annually with human parainfluenza virus infections. Current inactivated influenza vaccines are safe and somewhat effective, but they don't trigger sustained immune responses resulting in the need for yearly vaccinations. There is no vaccine currently available for human parainfluenza virus.
In the study researchers used reverse genetics to create an influenza A virus containing influenza and parainfluenza virus proteins. Mice were then infected with the virus and immunized with the recombinant vaccine. All mice receiving the vaccine developed antibodies and survived an otherwise lethal challenge with the influenza and parainfluenza viruses.
"This live bivalent vaccine has obvious advantages over combination vaccines, and its method of generation could, in principle, be applied in the development of a "cocktail" vaccine with efficacy against several different infectious diseases," say the researchers.
(Y. Maeda, M. Hatta, A. Takada, T. Watanabe, H. Goto, G. Neumann, Y. Kawaoka. 2005. Live bivalent vaccine for parainfluenza and influenza virus infections. Journal of Virology, 79. 11: 6674-6679.)