3 Nov 2010

BETHESDA, Maryland, November 3, 2010 – MVI's research and development strategy aims to build on the success of GlaxoSmithKline Biologicals' RTS,S vaccine candidate that is now in the final stages of development.

In looking toward the development of next-generation malaria vaccines with higher levels of protection, early clinical data strongly support using a “heterologous prime-boost” approach. Under this strategy, when a single application of a malaria vaccine is insufficient, repeated immunizations are performed using different vaccine preparations to sequentially stimulate a better immune response. Essentially, one vaccine primes the immune system to attack malaria while the next one boosts the response. Several prime-boost studies, all in early stages, show some promise.

MVI’s portfolio currently includes one prime-boost project, through a collaboration with Crucell, a Netherlands-based biopharmaceutical company, designed to deliver the circumsporozoite protein (CSP—the only malaria protein proven to induce a protective response in humans in field trials) to the immune system in a one-two punch, using two modified strains of a common cold-causing virus. The first cold virus is the delivery vehicle for the malaria protein and would get the immune system to mount a response just as it would to any cold-type virus, but it would incorporate a response to a malaria protein as well. Then, in an effort to increase the effect, the same protein is delivered again in a slightly different cold virus, thus stimulating the immune system to mount a second response. If this approach is found to work in humans, it could increase protection against malaria as compared with other vaccine candidates. The partners expect that clinical testing of this approach will take place at Seattle Biomedical Research Institute’s Malaria Clinical Trials Center in 2011.

At the Jenner Institute at the University of Oxford, director Adrian Hill’s prime-boost regimens “using simian adenoviral vectors [as the priming agent] and MVA expressing the clinically relevant Plasmodium falciparum ME.TRAP antigen have shown outstanding protective efficacy in mouse models.” Recently, Professor Hill observed similar immunogenicity in non-human primates. These results in monkeys are an indication of the potential of this vaccine approach.

Another prime-boost project that malaria vaccine experts are keeping an eye on is a collaboration between GlaxoSmithKline Biologicals and Crucell that will test Crucell’s Ad35 as the prime along with the RTS,S vaccine as the boost, testing an Ad35.CS prime/RTS,S-AS01 boost regimen in the clinic. The regimen is based on a non-human primate study published in 2007 in which an Ad35.CS prime, followed by two doses of RTS,S, generated equivalent antibody to RTS,S alone, but much higher CD4+ T cell responses than RTS,S alone or with other combinations of the two vaccines.

On Friday, November 5, 2010, researchers at the 59th annual meeting of the American Society of Tropical Medicine and Hygiene in Atlanta will present data on promising prime-boost strategies at a symposium sponsored by MVI. Beyond the scientific challenges, these scientists will outline the development and policy challenges that can be anticipated in implementing these more complex, multi-component vaccines in resource-limited settings. This symposium will focus on an array of prime-boost strategies that are yielding promising preclinical and clinical efficacy data, as well as the development and policy challenges that can be anticipated in implementing these more complex, multi-component vaccines.