"We are pleased to be able to tap into our existing HIV/AIDS clinical research infrastructure to help test promising investigational vaccines against TB," said NIAID Director Anthony S. Fauci, M.D. The sites are funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
The Phase II proof-of-concept study is testing the safety and effectiveness of an investigational booster TB vaccine developed by Aeras, a Rockville, Md.-based nonprofit organization focused on developing vaccines and other products to prevent TB, and Crucell N.V., a biopharmaceutical company based in the Netherlands.
The trial began in October 2010 and is now ongoing at three sites in Kenya, South Africa and Mozambique. It is sponsored by Aeras and receives funding from Aeras, Crucell and the European and Developing Countries Clinical Trials Partnership.
The trial, which will enroll HIV-uninfected infants ages 16 weeks to 26 weeks, is testing the AERAS-402/Crucell Ad35 candidate TB vaccine as a booster immunization to the current bacille Calmette-Guérin (BCG) TB vaccine. In countries where TB is highly endemic, the World Health Organization (WHO) recommends that all infants receive the BCG vaccine at birth. It is not routinely administered to infants in the United States. The BCG vaccine, first administered to humans in 1921, is the only licensed TB vaccine and reduces the risk of some forms of TB in children. However, it provides limited protection against adult pulmonary TB, the contagious and most common form of TB.
To allow for increased enrollment, the study is now being expanded to include up to six NIAID-supported clinical trial sites in sub-Saharan Africa. The first of these sites to join the trial is the Perinatal HIV Research Unit at the Chris Hani Baragwanath Hospital in Soweto, South Africa. The site is a member of several NIAID-funded clinical trials networks, including the HIV Vaccine Trials Network (HVTN), the HIV Prevention Trials Network (HPTN) and the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT). The HPTN is largely funded by NIAID with additional funding by the National Institute on Drug Abuse and the National Institute of Mental Health, all part of the NIH. IMPAACT is funded by NIAID and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, also part of the NIH.
Additional IMPAACT sites are expected to participate in the clinical trial when the next stage of enrollment opens in several months.
The AERAS 402/Crucell Ad35 vaccine is being given as a booster immunization to healthy infants who received the BCG vaccine at birth to determine if the investigational vaccine can increase protection against TB. The recombinant vaccine uses a live, non-replicating adenovirus (Ad35) to deliver three specific Mycobacterium tuberculosis antigens designed to stimulate the immune system and protect against TB. The vaccine does not contain live TB and cannot cause vaccinated infants to become infected with TB. The investigational vaccine had an acceptable safety profile in previous clinical trials among healthy adults and infants, as well as among HIV-infected adults and adults with latent TB.
The study was approved by ethics committees at each participating site as well as by national regulatory authorities in each of the participating countries. Additionally, an independent data and safety monitoring board regularly reviews the study data to ensure the protection of the study participants. Informed consent by a parent or legally authorized representative is required to enroll an infant into the study. The study is expected to be completed in 2015.
According to the WHO, in 2010 TB sickened 8.8 million people and killed 1.4 million people worldwide. It is a leading cause of death among people who are also infected with HIV. In Africa, there were an estimated 2.3 million TB cases and 254,000 TB deaths in 2010.