A Colorado State University research team has developed a novel vaccine to prevent tuberculosis, one of the world’s most deadly diseases. The vaccine triggers the body’s immunity in a novel way by activating specific immune system functions that enhance the response to the bacterium that causes tuberculosis.
Although in preliminary stages of testing, the vaccine would likely be effective against all strains of TB, including multi-drug and extensively drug resistant tuberculosis.
Preliminary evidence shows that the vaccine has promise of working after exposure to tuberculosis, which no other tuberculosis vaccine in current development has achieved. The vaccine is designed to be relatively easy to produce, unlike many of the vaccines under development.
"This novel vaccine system provides the template to design a series of new tuberculosis vaccines that could be very inexpensive to make," said Ian Orme, a professor in the Microbiology, Immunology and Pathology Department at Colorado State and head of the research team that developed the vaccine. "The next stage is to test the vaccine for long-lasting immunity and its ability to boost existing vaccines."
Human trials for the vaccine could occur in two to three years.
The vaccine is produced in a harmless bacterium that is closely related to the bacterium that causes tuberculosis. The vaccine contains two key proteins from the tuberculosis bacterium that are fused together. The vaccine triggers the immune response by attaching to specific receptors, called Toll receptors, on the surface of immune cells. These receptors are only responsible for recognizing tuberculosis and don’t play a role in recognizing other diseases; other vaccines do not target the immune system so specifically. This protects the body from subsequent exposure to TB infection.
"We have exploited new knowledge about how Toll receptors function in terms of how they turn on the immune response to develop an entirely novel way to approach tuberculosis vaccine design. This new approach could be adapted to multiple bacterial proteins we know are recognized by the immune response in people infected with this disease," Orme said.
"Usually, creating a vaccine involves two materials – the vaccine itself and a delivery agent called an ‘adjuvant.’ Adjuvants are often a complex mixture of chemicals that push the immune response to the vaccine. The problem here is that such mixtures are often fairly expensive to make. However, by building a vaccine that contains its own built-in ‘natural’ adjuvant, the Colorado State team was able to show that this vaccine did not need the additional chemical formulations for it to be effective."
Research collaborators at Colorado State’s Microbiology, Immunology and Pathology Department, part of Colorado State University’s College of Veterinary Medicine and Biomedical Sciences, include Dr. Baolin Wang, a visiting scientist from Shanghai, and Dr. Marcela Henao-Tamayo, a graduate student from Colombia.
Tuberculosis, once called consumption, is spread through the air when someone who is infected coughs or sneezes, and by sharing eating utensils.
Tuberculosis causes two million deaths worldwide and is the second most deadly infectious disease in the world, according to the Centers for Disease Control. Eight million new cases occur each year, and a growing number of people around the globe, including in the United States, are becoming infected with strains of the disease that are resistant to drugs, including strains that are resistant to multiple drugs.
Multi-drug resistant tuberculosis is up to 10 times more expensive to treat than infections that respond to traditional treatments, and patients with resistance often need treatment for three or more years. Side-effects of treatments can cause nausea, fatigue and impaired vision.
In addition, drug-resistant strains of tuberculosis have been identified by the National Institutes of Health as pathogens that could be intentionally introduced into population as a biological weapon.
Colorado State is one of the very few screening centers in the world searching for new drugs or vaccines that might be effective against tuberculosis, including strains that have developed resistance to current treatments. The university, which currently houses more than 100 faculty, staff and students researching tuberculosis, is a world leader in basic science leading to new preventive vaccines and medical treatments for the disease.
Tuberculosis is a focus of Colorado State University’s MicroRx, a first-of-its-kind enterprise to speed the transition of life-saving research on infectious diseases from the academic world into the global marketplace. MicroRx, unveiled in February, is just the first of the university’s Superclusters – alliances of academic researchers, economists and business experts designed to encourage collaboration and bridge the vastly different worlds of business and academia.
Since the 1960s, Colorado State University has engaged in infectious disease research and today is a world leader in researching vaccines, diagnostic tests, medications and ways to prevent the spread of infectious disease. Colorado State’s Foothills Campus, a global complex devoted to infectious disease research, is supported by more than $200 million in research funds from entities including the National Health Institute, Centers for Disease Control, NASA, Department of Homeland Security and the U.S. Department of Agriculture.