Tips from the Journals of the American Society for Microbiology

November 08, 2007

New Vaccine That Protects Monkeys Against Avian Flu Ready for Human Trials

Researchers from the National Institutes of Health and University of Maryland report that a new vaccine that protects monkeys against the avian influenza virus is now a candidate for clinical trial in humans. They report their findings in the November 2007 issue of the Journal of Virology.

The rate of transmission of the highly pathogenic avian influenza virus (HPAIV) from birds to humans is rapidly increasing. The H5N1 strain is responsible for 278 known human infections resulting in 168 deaths. The possibility of a pandemic outbreak emphasizes the need for an effective vaccine, however development has been impeded by factors such as poor immunogenicity, biosafety concerns, and risk of genetic exchange with circulating influenza virus strains.

In the study researchers developed a live vaccine incorporating the avian Newcastle disease virus (NDV), which expresses a common gene found in the H5N1 avian influenza virus, and tested it in African monkeys. The vaccine was administered both intranasally and through the respiratory tract in two doses with a 28-day interval in between. Response after one dose showed low amounts of virus shedding indicating protection. Following two doses, high levels of neutralizing antibodies were present in all immunized monkeys. A substantial response to either dosage was noted in the respiratory tract indicating a likely reduction in transmission in the event of an outbreak.

"In this study, we have developed a vaccine candidate, NDV-HA, for immunization against H5N1 HPAIV and have tested it in a nonhuman primate model," say the researchers. "The vaccine was well tolerated and induced substantial local and systemic immune responses, demonstrating that NDV has potential as a live virus candidate vaccine against HPAIV."

(J.M. DiNapoli, L. Yang, A. Suguitan Jr., S. Elankumaran, D.W. Dorward, B.R. Murphy, S.K. Samal, P.L. Collins, A. Bukreyev. 2007. Immunization of primates with a Newcastle disease virus-vectored vaccine via the respiratory tract induces a high titer of serum neutralizing antibodies against highly pathogenic avian influenza virus. Journal of Virology, 81. 21: 11560-11568.)

Researchers Identify a Promising New Class of Inhibitors Against West Nile Virus

Researchers from the Washington University School of Medicine have identified a new class of compounds that may inhibit West Nile virus in humans. They report their findings in the November 2007 issue of the Journal of Virology.

West Nile virus (WNV), a member of the flavivirus family which also includes dengue virus and yellow fever virus, can cause disease in humans, horses, and other vertebrate species when transmitted by infected mosquitoes. WNV has been confirmed in all 48 continental United States as well as Canada, Mexico, the Caribbean and South America and the fatality-to-case ratio calculated from recent outbreaks is 4 to 14%. There were 24,000 human cases diagnosed between 1999 and 2006 and currently there is no vaccine or therapeutic treatment approved for use in humans.

In the study researchers screened 80,000 small molecule compounds from a commercial library for their ability to inhibit WNV replication. They identified 10 compounds with strong inhibitory responses toward diverse WNV isolates. Many of these compounds had not been previously marked as inhibitory prospects against WNV or other related or unrelated viruses. In addition several of the compounds also showed inhibition capabilities against dengue and yellow fever viruses.

"Overall, these compounds comprise a novel class of promising inhibitors for therapy against WNV and other flavivirus infections in humans" say the researchers.

(A.O. Noueiry, P.D. Olivo, U. Slomczynska, Y. Zhou, B. Buscher, B. Geiss, M. Engle, R.M. Roth, K.M. Chung, M. Samuel, M.S. Diamond. 2007. Identification of novel small-molecule inhibitors of West Nile virus infection. Journal of Virology, 81. 21: 11992-12004.)

New Study Suggests Many Unknown Microbes in Soil

Metagenomic analysis of microbial biodiversity in soil samples suggest that non-bacterial species greatly outnumber bacterial species. This means the majority of microorganisms on the Earth remain undiscovered, according to researchers from the University of Colorado, University of South Florida, San Diego State University and Duke University. They report their findings this month in the journal Applied and Environmental Microbiology.

Soil microorganisms represent a significant portion of living matter on Earth and play a key role in ecosystem functions. Bacteria, fungi, archaea and viruses are the four microbial groups currently known to man. Bacterial presence in soil has been the most extensively studied, however with the environment at the forefront of worldwide focus, expanded research on fungal, archaeal, and viral communities is much needed.

In the study researchers used an RNA-based analysis technique to examine the richness of bacteria, fungi, archaea, and viruses in samples collected from prairie, desert, and rainforest soils. These sites were specifically targeted because they represent globally dominated ecosystem types and are broad in aridity and productivity. Results showed that unique archaeal or fungal units appeared to rival or exceed unique bacterial units in each of the soil samples.

"In this first study, to comprehensively survey rival communities using a metagenomic approach, we found that soil viruses are taxonomically diverse and distinct from the communities of viruses found in other environments that have been surveyed using a similar approach," say the researchers. "Within each of the four microbial groups, we observed minimal taxonomic overlap between sites, suggesting that soil archaea, bacteria, fungi, and viruses are globally as well as locally diverse."

(N. Fierer, M. Breitbart, J. Nulton, P. Salamon, C. Lozupone, R. Jones, M. Robeson, R.A. Edwards, B. Felts, S. Rayhawk, R. Knight, F. Rohwer, R.B. Jackson. 2007. Metagenomic and small-subunit rRNA analyses reveal the genetic diversity of bacteria, archaea, fungi, and viruses in soil. Applied and Environmental Microbiology, 73. 21: 7059-7066.)

American Society for Microbiology

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