The Netherlands Ministry of Foreign Affairs has renewed its funding to the Aeras Global TB Vaccine Foundation with a pledge of €11.7 million over four years (2011–2014). The money will be used to further efforts to develop vaccines for tuberculosis (TB).
Aeras’ first grant from the Netherlands Ministry of Foreign Affairs, which was for €18.7 million, came in 2006. Aeras says that since then four of its TB vaccine candidates have moved into clinical trials in Europe, North America, and Africa. Two of these are at the Phase II stage and will enroll infants in South Africa, Kenya, Uganda, and Mozambique.
“The forward movement of TB vaccine candidates in the development pipeline owes a great deal to the generous support of the Dutch Ministry of Foreign Affairs and the people of the Netherlands,” remarks Jim Connolly, president and CEO of Aeras.
The currently available vaccine, Bacille Calmette-Guérin, provides some protection against pediatric TB but is unreliable in protecting adult pulmonary TB, the most common form of the disease, Aeras points out. The company is collaborating and facilitating research in conjunction with academic scientists as well as industry and government organizations to develop safer and more immunogenic TB vaccines. Aeras notes that, globally, nine TB vaccine candidates are in clinical testing, which includes its own four investigational vaccines.
Aeras’ lead candidate is MVA85A, a booster TB vaccine for infants and adolescents developed by the University of Oxford. The university utilized a recombinant modified vaccinia virus Ankara (MVA) as its vaccine delivery system.
MVA85A has successfully gone through Phase I trials in the U.K., Gambia, and South Africa as well as Phase II trials in South Africa and Gambia. Aeras is sponsoring a Phase IIb trial in 2,784 infants in partnership with University of Cape Town's South African Tuberculosis Vaccine Initiative (SATVI) in Worcester, South Africa. The proof of concept trial in infants began in April 2009.
Also at the Phase II stage is Aeras-402, an adeno vectored vaccine developed by Crucell that contains M. tuberculosis antigens 85A, 85B, and TB10.4. The Adenovirus 35 vector was also chosen for TB vaccine work because there is relatively little pre-existing neutralizing antibody directed against this virus in humans in developing countries, Aeras notes.
Three Phase I trials of this candidate conducted in the U.S. are completed, and other Phase I and II trials are in progress in South Africa, Kenya, and the U.S. A Phase II study in adults who have been exposed to TB is in progress in South Africa. The first stage of a Phase II multicenter trial in healthy infants is in progress in Kenya and will expand to Mozambique, Uganda, and South Africa in 2011.
Next in Aeras’ line-up is the GSK-developed GSK M72, an immunogenic fusion protein. It recombines two proteins identified in human and animal studies over a 10-year period and uses GSK adjuvants. A Phase I trial of this candidate in Belgium is completed. This trial compared M72 formulated in different adjuvants to determine the optimal formulation.
Volunteer screening for a Phase II study started in March 2008 in Worcester, South Africa. With support from Aeras and led by SATVI, GSK M72 will undergo testing in a randomized study in 45 healthy adults previously vaccinated with Bacille Calmette-Guérin.
Aeras’ fourth clinical vaccine candidate for TB is Aeras-404, which was originally developed by The Statens Serum Institut (SSI). In 2008, Sanofi Pasteur became a development partner on this candidate. It is also a fusion protein like GSK M72 and uses SSI's HyVac4 antigen, which is another fusion protein of 85B and TB10.4, combined with Intercell's IC31 adjuvant. It is in Phase I trials located in Finland, South Africa, and Sweden.