New TB vaccine enters clinical testing

(Press-News.org) Rockville, MD, USA and Tallinn, Estonia (September 23, 2010) – At an international gathering of TB vaccine researchers in Tallinn today, the Aeras Global TB Vaccine Foundation announced it will initiate a clinical trial of an investigational live recombinant tuberculosis vaccine to be led by researchers at Saint Louis University in St. Louis, Missouri, USA. The announcement was made at the Second Global Forum on TB Vaccine Development.

Building on more than a decade of global scientific research, Aeras scientists have engineered a new investigational vaccine, called AERAS-422, which will undergo clinical trials to evaluate its properties for interrupting TB at all stages of infection, including initial infection, latency and reactivation.

"Moving our lead in-house vaccine from the laboratory into clinical testing is an important milestone for Aeras and its partners. Finding a potential replacement for the currently available TB vaccine, which was invented almost 90 years ago, is a primary goal in our mission," said Thomas G. Evans, MD, Aeras' Chief Scientific Officer. "Based on data from pre-clinical studies, we are cautiously optimistic about the potential of this vaccine candidate to be safer and more immunogenic than the currently available vaccine."

The new vaccine, called AERAS-422, is a modernized version of the currently used TB vaccine – Bacille Calmette Guérin (BCG). BCG is widely viewed as insufficient in preventing pulmonary TB, and this trial is part of a wider global effort to develop safer and more immunogenic TB vaccines that would be effective against all forms of TB.

AERAS-422 has been modified with an endosome escape mechanism and over-expresses three key proteins: 85A, 85B and Rv3407. The bacterium that causes TB hides inside cells. Therefore, the endosome escape mechanism is designed so that the proteins will escape an internal compartment of the cell and be more efficiently presented to the immune system to elicit a greater protective response in the body.

"The TB epidemic continues to become more complex and difficult to control, especially in South Africa where resistance to available TB treatments is on the rise," said Bernard Fourie, PhD, Chief Scientific Officer of Medicine in Need and Managing Director of Mend South Africa. "The scientific community has made developing a safer and more effective TB vaccine a priority and we are pleased that there is progress in the field."

The Phase I clinical trial to test the safety of AERAS-422 will be led by Principal Investigator Daniel Hoft, MD, PhD, at Saint Louis University's Center for Vaccine Development. The trial will enroll healthy adults who have never received a vaccination against tuberculosis. Dr. Hoft's team will also conduct initial immunological assessments.

"The TB vaccine field has made tremendous progress over the past 10 years," said Daniel Hoft, MD, PhD, of the Center for Vaccine Development at Saint Louis University. "Not only is the start of the clinical trial of AERAS-422 another important benchmark in the search for more effective TB vaccines, it is also an opportunity to learn more about cellular immunity, a less well understood but critically important component of TB vaccine development."

Aeras is pursuing a TB vaccine development strategy based on a prime-boost approach that incorporates an initial BCG or recombinant BCG vaccination for infants at birth to be followed by a booster vaccine later in infancy to adolescence. In addition to AERAS-422, developed as a "prime," Aeras is also supporting the clinical development of four TB vaccine candidates designed as "boosters" in the prime-boost vaccine scenario. Two have reached the Phase IIb proof of concept stage.

### About Tuberculosis

Tuberculosis is the world's second deadliest infectious disease, with nearly 9.3 million new cases diagnosed in 2007. According to the WHO, an estimated 1.8 million people died from TB in 2007. One-third of the world's population has been infected with the TB bacillus and current treatment takes 6𔃇 months. The current TB vaccine, Bacille Calmette-Guérin (BCG), developed almost 90 years ago, reduces the risk of severe forms of TB in early childhood but is not very effective in preventing pulmonary TB in adolescents and adults — the populations with the highest rates of TB disease. TB is changing and evolving, making new vaccines more crucial for controlling the pandemic. Tuberculosis is now the leading cause of death for people living with HIV/AIDS, particularly in Africa. Multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) are hampering treatment and control efforts.

About Aeras

The Aeras Global TB Vaccine Foundation (www.aeras.org) is a non-profit research organization developing new tuberculosis vaccines and ensuring that they are distributed to all who need them around the world. Aeras is funded primarily by private foundations and government aid agencies. Aeras is based in Rockville, Maryland, where it operates a state-of-the-art manufacturing and laboratory facility, and Cape Town, South Africa.

About the Center for Vaccine Development at Saint Louis University

The Center for Vaccine Development at Saint Louis University (http://medschool.slu.edu/vaccine/) is a multi-disciplinary research center designed to conduct basic and clinical research on new vaccines and biologics. The Center has demonstrated its ability to recruit large numbers of volunteers and participate in protocols with a wide variety of research designs, vaccine candidates, and subject populations, and has a strong record of cooperating with the National Institute of Allergy and Infectious Diseases (NIAID), other vaccine evaluation units, outside investigators, and industry.