A pilot study at Saint Louis University Center for Vaccine Development could shape the future of tuberculosis vaccine research by developing tests to identify the most promising vaccine candidates to address this global health crisis.

"Our goal is to save lives faster," said Daniel Hoft, M.D., Ph.D., director of the division of infectious diseases, allergy and immunology at SLU. "We hope to develop a process that will allow us to screen new TB vaccines for inducing immunity in people, which will get us on the right research track faster and save valuable research dollars."

It's critical to find a vaccine to protect people from tuberculosis, which the World Health Organization has declared a global health emergency. The Mycobacterium tuberculosis pathogen that causes TB is one of the world's deadliest infectious agents, costing an estimated two million lives a year. Further, treating the illness is becoming increasingly difficult because new strains of TB do not respond to antibiotics.

The current TB vaccine that is given to infants in countries other than the U.S. was developed more than 60 years ago and is known as BCG (Bacillus Calmette-Guérin). Made from a weakened strain of live bacterium from cows, the vaccine protects babies from the worst forms of TB. However, it does not protect adolescents and adults from pulmonary TB, which accounts for most cases of the disease, or protect people from the progression of tuberculosis bacteria that lies dormant in the body before it turns into active disease in 10 percent of carriers.

According to Aeras, a multi-national non-profit organization dedicated to developing effective TB vaccines and treatments, conducting the scientific testing on the safety and effectiveness of a vaccine takes between 13 and 16 years before the vaccine can be licensed and available in the marketplace.

Information from Aeras notes the direct cost to develop a single TB vaccine for one specific target group could be as high as $315 million. The lion's share of the research cost -- up to $265 million -- is for a phase III efficacy trial that could include many thousands of people and lasts about four years. A phase III study is the final step in the research process before a vaccine can be licensed for use.

Hoft said TB vaccine research is complicated partly because so many people carry the TB bacteria and never develop disease. In addition, there is not an ideal animal model for testing TB vaccines, a necessary step before they are given to human volunteers.

Hoft is not testing a specific vaccine; rather he is testing the vaccine testing process through a challenge screening protocol. A challenge protocol "challenges" the body's immune system to see if it can mount a response that fights against a foreign invader.

His pilot study, supported by a $100,000 University grant, is designed to answer a number of questions including what assays provide the most information about whether or not a vaccine is triggering a strong immune response and when those tests are best conducted.

"We want to know if we can develop a protocol that will be reproducible so we can use small groups of volunteers to see how different vaccines work," Hoft said.

He plans to administer the current BCG vaccination against tuberculosis as a shot right underneath the skin. Participants may develop a temporary lesion at the site, and may shed BCG bacterium, which shows the organism is alive and growing.

Researchers then will use a number of tests to monitor the amount of shedding in real time, to see which works best to measure the body's response to infection and identify when the response is most robust. They also will compare the results of various blood tests to measure the body's inflammation response and quantify the numbers of genomes of BCG by conducting sophisticated analysis to tell how the expression of the BCG gene changes over time.

"Our hope is that these tests will help us develop new TB vaccines," Hoft said. "We want to see if there's a pattern to shedding, which could help us pinpoint a time that is best to look for a strong immune response. We're trying to develop the optimal protocol to detect immunity in people, based upon detecting a protective immune response that prevents BCG shedding after the challenge."

The pilot study, which lasts about six months, will include up to 20 participants who are between 18 and 45 years old.