DiagnosticsNew Collaboration To Conduct A Clinical Trial Of TB Vaccine Candidate In People Living With HIV
The Aeras Global TB Vaccine Foundation (Aeras) has announced a new collaboration with The Aurum Institute on the first study to test the AERAS-402/Crucell Ad35 tuberculosis (TB) vaccine candidate for safety in people living with the human immunodeficiency virus (HIV). Aurum will conduct this trial in people living with HIV at its clinical trial site near Johannesburg, South Africa. The Medicines Control Council of South Africa and two Independent Ethics Committees in South Africa have given approval to test the vaccine in South Africa. AERAS-402/Crucell Ad35 has been previously tested for safety in healthy adults in the United States and HIV-negative adults and infants in South Africa.
"TB/HIV is a devastating problem in South Africa and many other countries, and it is essential that new tuberculosis vaccines protect people living with HIV," said Jerald C Sadoff, President and CEO of the Aeras Global TB Vaccine Foundation. "Aurum is a world-class organisation dedicated to TB/HIV research and health systems management, and we are pleased to be working with them to move forward this promising vaccine candidate in a population at increased risk of getting sick and dying from TB."
Preliminary but promising clinical trial data indicate that AERAS-402/Crucell Ad35 has produced the highest levels of CD8 immune cells ever seen in trials of any TB vaccine. Inducing CD8 cellular immunity is one of the leading strategies experts are pursuing to develop vaccines that will be effective against TB.
Tuberculosis is the leading cause of death among people living with HIV in Africa and Asia. People with HIV living in countries with high TB prevalence are 20 times more likely to develop TB than those who are HIV-negative. According to the World Health Organization"s (WHO) 2009 TB surveillance report, one in four TB deaths globally is HIV-related, twice as many as previously recognised. In 2007, there were an estimated 1.37 million new cases of TB among people living with HIV and 456 000 deaths. Seventy-three percent of people with TB in South Africa are co-infected with HIV. A vaccine to prevent TB is needed for people with and without HIV.
"We believe that an effective TB vaccine is the best hope for the achievement of the millennium goals for TB reduction and the eventual elimination of this scourge from our planet," said Prof Gavin Churchyard, CEO of The Aurum Institute. "We are delighted to be partnering with Aeras in this key study en route to that era."
The safety of volunteers is of paramount importance, and all trials will adhere to the highest international standards of safety and ethics, including informed consent. Extensive safety information has already been collected about this candidate vaccine. Preclinical toxicology studies demonstrated safety in animals, and AERAS-402/Crucell Ad35 has been tested in seven clinical trials between 2006 and the present without a single serious adverse event related to the vaccine candidate reported.
AERAS-402/Crucell Ad35 trials
A Phase I small safety clinical trial launched in October 2006 in Kansas, USA indicated that the vaccine candidate is safe in healthy adults who have not previously been immunised with Bacille Calmette-Guçİrin (BCG), the only currently licensed TB vaccine, in the USA.
Data from a second Phase I study, started in May 2007 in South Africa, demonstrated induction of both critical arms of the cellular immune system, CD4 and CD8 immune T-cells, and showed that in those participants who responded, CD8 immune responses were much higher than had previously been seen in a TB vaccine study.
A third Phase I study in healthy adults in St. Louis, Missouri, USA was launched in December 2007 focusing on the immunogenicity (immune response) and safety of two AERAS-402/Crucell Ad35 boost doses, administered at three to six month intervals after BCG priming in healthy adults. Data from this study indicate that two injections of AERAS-402/Crucell Ad35 are immunogenic; these responses and those seen in South African adult volunteers who had been vaccinated with BCG around birth are some of the highest CD8 T-cell responses ever seen in a TB vaccine study. This immune response is greater than that detected in the absence of BCG prime, supporting the possible utility of AERAS-402/Crucell Ad35 as a booster vaccine. BCG prime alone shows limited immunogenicity.
An ongoing study in St. Louis, Missouri, USA is evaluating a longer prime-boost interval. Enrollment for the study has been completed, and there are no significant safety issues.
A Phase I clinical trial of AERAS-402/Crucell Ad35 was started in Kenya in October 2008. The study was conducted by the KEMRI/Walter Reed Project-Kisumu at their Kombewa Clinical Trials Centre near Kisumu, in Western Kenya. Its main objective was to test the safety of the candidate vaccine in adults who had been vaccinated with BCG and who have or do not have latent TB infection. This study is now complete, and specimen and data analysis is ongoing. No significant safety issues have been identified.
In October 2008, enrollment for the first Phase II study of AERAS-402/Crucell Ad35 began in Cape Town, South Africa. The study is being conducted by the University of Cape Town"s Lung Institute in collaboration with the South African Tuberculosis Vaccine Initiative. The candidate is being tested in 82 adults who have had active TB. No significant safety issues have been identified.
A Phase I clinical trial of the vaccine candidate was started in South Africa in April 2009, with the objective to test AERAS-402/Crucell Ad35 in infants. The trial participants are 54 healthy infants who have not been exposed to TB or HIV.
Annmarie Leadman
Aeras Global TB Vaccine Foundation