Aeras Global TB Vaccine Foundation

The Aeras Global TB Vaccine Foundation is a non-profit Product Development Partnership (PDP) dedicated to the development of effective tuberculosis vaccine regimens that will prevent TB infection in all age groups and will be affordable, available and adopted worldwide. Founded in 2003, Aeras is located in Rockville, Maryland, USA.

Mission

Aeras' mission is to develop, test, characterize, license, manufacture and distribute at least one new TB vaccine regimen for infants and another for adolescents within 7-10 years and ensure its availability to all who need them.

Objectives

Aeras has three main objectives. First, to advance the world's leading TB vaccine candidates forward towards licensure and availability by reviewing data from clinical trials and selecting only the most promising candidates for large-scale Phase III trials. Second, to rationalize the TB vaccine development process by attempting to validate animal models and immunologic markers capable of predicting vaccine induced protection in humans, which will make expedite development of more effective vaccines in the future. And third, to maintain a robust TB vaccine pipeline so that subsequent generations of better vaccines that prevent reactivation of latent infection will be brought forward.

Funding

Aeras receives funding from a number of donors. The Bill and Melinda Gates Foundation recently announced $200 million grant to continue research for the next five years and has been the foundation's primary donor since its inception [ [http://www.gatesfoundation.org/GlobalHealth/Pri_Diseases/Tuberculosis/Announcements/Announce-070918.htm Bill and Melinda Gates Press Release] ] . The Centers for Disease Control, the Danish International Development Agency, the Netherlands Ministry of Foreign Affairs, and the Research Council of Norway also provide funding.

Vaccine Development

Aeras currently has six vaccines in its pipeline, two of which are being manufactured at Aeras headquarters. The other four are being produced in collaboration with Aeras' partners throughout the world.

Aeras believes the most effective vaccine regimen will utilize the "prime-boost" strategy of vaccination. This involves an initial “prime” inoculation given at a very young age, followed by a “boost” given some time later. It is hoped that this strategy will not only increase the quality of protection, but will extend the duration of protection as well [Xing Z, Charters TJ. Heterologous boost vaccines for bacillus Calmette-Guérin prime immunization against tuberculosis. 2007 Aug;6(4):539-46.] .

Using the prime-boost regimen as the guiding principle of its discovery work, Aeras has made creating a modern version of the existing BCG its highest priority. By genetically modifying the existing strain, Aeras has created several recombinant BCGs, including AERAS-407, that overexpress selected antigens and promote endosome escape, thereby enhancing immunogenicity. Antigen overexpression has been validated in proof of principle studies in humans, where the resulting rBCGs induced higher levels of functional antigen specific T cells than its parent BCG [Sadoff, Jerry. Advances in Tuberculosis Vaccine Strategies. Nature Reviews Microbiology. Vol. 4. June 2006.] . Additionally, in non-human primate studies, Aeras has demonstrated that endosome escape vaccines that also overexpress TB antigens induce increased cellular responses compared to the current BCG. These recombinant BCG strains have also demonstrated increased safety in immuno-compromised animals, suggesting that they will have a better safety profile in humans - an aspect especially pertinent for potential use in HIV positive patients.

Trial Sites

In preparation for large-scale vaccine trials, Aeras has developed study sites at several locations worldwide. These locations, in Worcester, South Africa; Kampala, Uganda; Kisumu, Kenya; and Bangalore, India; all have extremely high incidence and prevalence rates of TB and are thus well-suited for Phase I-III trials [ [http://www.who.int/tb/publications/global_report/2008/chapter_1/en/index3.html World Health Organization Global TB Report 2008] ] . At each site, Aeras has developed a Professional Development Program to boost the community health-care infrastructure. All members of the local research team are provided with a core foundation of knowledge and skills in the management of clinical trials and infectious diseases. To date, over 300 participants have completed the program. Additionally, Aeras works with South African Tuberculosis Vaccine Initiative and the George Washington University to provide further training and the construction of modern laboratory and health facilities at each site.

External links

* [http://www.aeras.org The Aeras Global TB Vaccine Foundation]
* [http://www.gatesfoundation.org The Bill and Melinda Gates Foundation]

References