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NIH Grant Of $5.6 Million Awarded To USU Researchers To Fight Deadly Viruses

Main Category: Infectious Diseases / Bacteria / Viruses
Also Included In: Immune System / Vaccines;  Biology / Biochemistry
Article Date: 30 Jun 2008 - 0:00 PDT

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Researchers at the Uniformed Services University of the Health Sciences (USU) have been awarded a $5.6 million grant from the National Institute of Allergy and Infectious Diseases (NIAID) to develop and test vaccines and treatments for the deadly Nipah and Hendra viruses.

Christopher C. Broder, Ph.D., USU professor of microbiology and immunology and director of the university's interdisciplinary program in Emerging Infectious Diseases, is the principal investigator of the grant from NIAID. The grant was awarded to continue work on vaccines and therapeutics for Nipah and Hendra that his group has been working on for the past several years. The award will support a continued collaboration with investigators at Australia's Commonwealth Scientific and Industrial Research Organization (CSIRO) Livestock Industries, Australian Animal Health Laboratory (AAHL) and Australian Biosecurity Cooperative Research Center (AB-CRC) in Geelong, Victoria.

Hendra and Nipah are recently emerged paramyxoviruses that are highly pathogenic and can cause lethal infections in several animals and in humans. Since their initial discovery in Australia and Malaysia, sporadic Hendra outbreaks have been reported from 1995 to 2007, while Nipah has caused at least nine outbreaks between 1998 and 2008. Human case fatality rates have approached 75 percent, and there has been evidence of human-human transmission. The most recent appearance of Nipah in 2008 claimed the lives of several children.

In earlier work, Katharine Bossart, Ph.D., a former graduate student in Broder's laboratory who now works with the Australian Animal Health Laboratory in Geelong, developed a subunit vaccine for Nipah and Hendra composed of a piece of the virus known as the G glycoprotein. In other recent studies, Broder's group, in collaboration with researchers from the National Cancer Institute, developed a potent Nipah and Hendra virus neutralizing human monoclonal antibody (m102.4).

"We now have the critical resources needed to evaluate the therapeutic potential of both vaccines and perhaps more importantly a potent human antibody against both Nipah virus and Hendra virus, that could help control outbreaks in geographical regions susceptible to these emerging viruses, and result in a real benefit to those people at risk of infection and disease caused by these deadly agents," said Broder.

Previously, Broder and colleagues demonstrated that a cell surface protein called Ephrin-B2 is a functional receptor for both the Hendra and Nipah viruses. Ephrin-B2 is highly conserved in animals, and this finding shed light on how the viruses can infect such a wide range of hosts. The receptor is found on cells in the central nervous system, as well as in cells lining blood vessels. It is essential for central nervous system development and blood vessel growth in the embryos of humans and other mammals.

The research has led to four inventions on which USU and HJF have filed patent applications. The first patent application, "Soluble forms of Hendra Virus and Nipah Virus G glycoprotein," covers the production and use of a recombinant soluble G glycoprotein. This protein has utility as a vaccine, in the development of pharmaceutical compositions and in diagnostic assays.

The second patent application, "Compositions and Methods for the Inhibition of Membrane Fusion by Paramyxoviruses," covers the use of a novel peptide sequence of the soluble F glycoprotein, to block fusion of the virus with the host cell. This peptide can be used as a prophylactic, and/or to treat infections, and antibodies developed using this peptide can be utilized in diagnostic assays.

A third patent application, "Soluble forms of Hendra and Nipah Virus F glycoprotein" covers the production and use of a new recombinant soluble F protein." The remaining patent application, "Human Monoclonal Antibodies Against Hendra and Nipah," filed in conjunction with the National Institutes of Health, covers the production and use of monoclonal antibodies which could be used as a therapeutic for people already infected with the disease.

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Article adapted by Medical News Today from original press release.
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Source: Mark Scher
Henry M. Jackson Foundation for the Advancement of Military Medicine




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