A Good Vaccine Is Hard to Find: Nonprofit Biotechs Tackle Tuberculosis

Abstract

The Aeras Global TB Vaccine Foundation was founded in 2003 as a spinoff of Maryland BIOTECH Sequella. The 130 person nonprofit biotech intends to develop a TB vaccine by 2016. “The word everybody uses in the nonprofit TB drug field is accessibility,” said Peg Willingham. “People have got to afford them, or have somebody pay for them, so that they can afford the therapies.”In 2007, The Gates Foundation awarded Aeras $200 million over 5 years to push a TB vaccine through phase II, building on a 2003 grant. Aeras estimates it will cost $120 million to bring a TB vaccine candidate to phase III trials. Aeras has six vaccine candidates in the pipeline, two in preclinical, two in phase I/II, and one in phase II.“Our ideal would be a vaccine that would prevent initial infection and later reinfection,” said Willingham. “At a minimum … it should be 60% effective. No vaccines on the market are 100% effective.” Production has to scale very cheaply to 100 million doses a year. To that end, Aeras has its own in-house vaccine manufacturing facility.“Our strategy is called a prime boost strategy,” said Dr. Lewellys Barker, senior medical advisor. Aeras is developing an improved BCG vaccine for newborns. According to Barker, BCG is a live vaccine, and Aeras's goal is to modify it so it overexpresses certain antigens to make it safer, particularly for patients with HIV. Long-term follow-up studies suggest that TB vaccine protection doesn't last, so a booster is necessary.Aeras, along with Nevada-based Crucell, has developed AERAS-402/Crucell Ad35, a replication-deficient adenovirus that expresses TB antigens meant to elicit high levels of CD8+ T cell responses. AREAS-402/Crucell AD35 completed a phase I clinical trial in the US in 2006. Another phase I trial started in South Africa in 2007 in healthy adults vaccinated at birth with BCG.Aeras is currently partnering with the South African Tuberculosis Vaccine Initiative of the University of Capetown (http://www.satvi.edu) to test the Oxford University MVA viral-vector vaccine. According to Willingham, South Africa has good technical capabilities and infrastructure. It also has a high rate of endemic TB, which is necessary for testing the vaccine in large and varied populations to get significant data. Aeras also has agreements in Kenya, India, Uganda, and Cambodia.“First we have to get a vaccine that works well,” said Barker. “And that is the challenge in TB. We don't know what kind of immune response we need to get for a recipient to be protected.” According to Barker, cell-mediated responses are thought to be important, but the role of antibodies is unknown. A major accomplishment will be the ability to gauge T cell responses. “Aside from a better regime for immunizing against TB, we would like it to work for people infected with HIV,” Barker said.Aeras also has a few preclinical projects: an oral vaccine using a bacteriophage capsid inserted in attenuated shigella bacteria as well as an inhaled vaccine being tested on animals at Tulane University in New Orleans. Barker noted that it is uncertain whether animal tests could predict vaccine performance in people or what would be the indication of the immune response needed for animals. Researchers do not know what immune response is needed to judge the effectiveness of early childhood immunization. “Clinical testing will be difficult, as diagnosis of TB in early childhood is difficult,” said Barker.“We have relatively little drug-resistant TB in this country, but this not really true in the rest of the world,” said Barker.