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Brucellosis vaccine to be developed by researchers

By Jeff Douglas

Spectrum Volume 17 Issue 09 - October 20, 1994

A team of researchers in the Virginia-Maryland Regional College of Veterinary Medicine (VMRCVM) has been awarded a $415,000 grant from the United States Army Medical Research and Development Command to develop a vaccine which will protect people from brucellosis.

Brucellosis, a disease which causes severe illness and death in livestock and humans, is largely controlled in the United States and western Europe, yet it remains a significant threat in Africa, the Middle East, South America, and other developing areas of the world.

Considered a zoonotic disease, one which is transmissible from animals to humans, brucellosis can be caught from eating undercooked meat and unpasteurized dairy products from infected animals, or by handling infected tissues. In humans, it causes undulant fever, characterized by malaise, aches and fevers which can soar to 103-104 degrees.

The Army's goal is two-fold, according to Gerhardt Schurig, director of the college's interdisciplinary Center for Molecular Medicine and Infectious Diseases (CMMID), which is home to one of the nation's leading research programs into brucellosis, a bacterial disorder caused by the Brucella abortus organism.

First, a human vaccine is required to protect American troops stationed in areas of the world where the disease is indigenous. Second, brucellosis could be used as a biological-warfare agent.

Immunologists, virologists, bacteriologists and molecular biologists working collaboratively in the center have already developed a new vaccine for domestic animals and wildlife based upon a mutant strain of Brucella abortus called RB51, which was discovered by Schurig in 1982.

The mutant strain RB51 vaccine, which was trademarked by Virginia Tech Intellectual Properties in 1992, is unable to cause disease and has major serological advantages over existing vaccines. One of the most important is that it is precise enough so that vaccinated animals may be distinguished serologically from infected animals, a feature which enables producers to avoid costly over-condemnations.

Funded by the United States Army Medical Research and Development Command at Fort Dietrick, Md., the three-year grant will support efforts to identify the protective antigen on the brucella organism, define the genes which code for the creation of these antigens, and then express these genes in the vaccinia virus to create a vaccine that will confer protective immunity.

The vaccinia virus, which was used in the development of the vaccine used to eradicate smallpox, is an approved human vaccine-delivery system.

The grant should also enable the researchers to make important progress in other areas of brucellosis research, according to Schurig. While the antigens that confer protective immunity will be expressed in the vaccinia virus, the work under way in the CMMID may enable the researchers to create an even more effective vaccine by increasing the immunogenicity of the brucella organism itself.

In 1993, the investigators signed a Cooperative Research and Development Agreement with the Department of Bacterial Diseases at Walter Reed Army Institute of Research, which creates a formal structure for sharing research information and biological agents.

While Virginia has been declared brucellosis free, several states, including Florida, Texas, and Louisiana, still have significant problems.

The VMRCVM has conducted nearly $1,000,000 worth of research into brucellosis over the past 10 years, and has received five major grants from the USDA and other funding agencies.

Faculty members participating in the project include Schurig, an immunologist; molecular biologist Stephen Boyle, bacteriologist Nathan Sriranganathan, and virologist Thomas Toth. The center plans to hire two post-doctoral researchers to assist with the project.

The CMMID was established four years ago to focus on the development of vaccines and diagnostic tests for infectious diseases using, among others, genetic engineering technologies. CMMID researchers believe the grant was awarded to the multi-disciplinary center because of the unique way it promotes collaboration among diverse scientific disciplines.

CLARIFICATION printed in the 10/27/94 issue of Spectrum