15 Feb 2011

Project exploits breakthrough technology in producing protein targeting parasite sexual development while expanding malaria vaccine manufacturing capacity in developing world.

WASHINGTON DC, February 15, 2011 – The PATH Malaria Vaccine Initiative (MVI) announced today an innovative collaboration with experts at the Tulane University School of Public Health and Tropical Medicine and India’s Gennova Biopharmaceuticals Ltd. to produce and perform pre-clinical testing of a vaccine formulation intended to block the transmission of the malaria parasite from mosquitoes to humans.

The project deepens MVI’s commitment to combating malaria on multiple fronts—with vaccines that protect against clinical disease and vaccines that disrupt the parasite’s life cycle—while engaging new partners in emerging markets. 

Transmission-blocking vaccines, though not yet widely tested in humans, are attracting widespread interest due to their potential to be used in conjunction with more traditional malaria vaccines and other interventions—such as malaria drugs and bed nets—to make gradual elimination and even eradication of the disease a reality. Malaria kills nearly 800,000 people every year, most of them children under the age of five.

"We’re investing in developing transmission-blocking malaria vaccines to support two long-term goals: introducing an 80 percent efficacious malaria vaccine by the year 2025 and eventually eradicating malaria altogether," said Dr. Christian Loucq, director of MVI. "A vaccine that breaks the cycle of malaria transmission will be important to our success."

Dr. Nirbhay Kumar, professor of tropical medicine at Tulane, is working on a novel approach that targets a specific, but hard-to-synthetically-produce protein that the malaria parasite needs to spawn in the mosquito host. Using the protein or antigen—known as Pfs48/45—in a vaccine could potentially induce an immune response capable of slowing or halting disease transmission by preventing the parasite from re-infecting mosquitoes after feeding on an infected person. The malaria parasite’s survival depends on its ability to constantly alternate between human and mosquito hosts, so effectively blocking its ability to complete its life cycle should lead to a systematic decline in malaria cases. Transmission-blocking vaccines are viewed as an important intervention to support future malaria eradication efforts.

However, a major barrier to evaluating the vaccine potential of Pfs48/45 has been the inability to effectively manufacture the antigen—antigens are substances that trigger immune responses—in the necessary quantity and form. In 2009, Kumar and colleagues at Johns Hopkins University, the Walter Reed Army Institute of Research, and Kenya’s Institute of Primate Research published a study announcing that they had successfully produced a purified form of the protein and that it generated “potent malaria transmission-blocking antibodies” when tested in mice and baboons. 

"With MVI’s support we now can work with Gennova to produce sufficient quantities of the protein and develop a variety of vaccine formulations that can be tested in animals to see which ones give us the strongest immune response," Kumar said. "We also plan to take blood from the immunized animals and feed it to mosquitoes in the laboratory to assess its capacity to interfere with the parasite life cycle leading to blocking of malaria transmission."

"We are eager to use our expertise and technical capacity to accelerate testing of this intriguing approach to malaria control," said Dr. Sanjay Singh, CEO of Gennova and formerly with the Malaria Vaccine Development Unit at the US National Institutes of Health. "We understand the importance of reliable manufacturing capacity worldwide to making malaria vaccines a reality and the need for new tools to fight this often deadly and always incapacitating disease."

While most malaria deaths occur in Africa, a study in October 2010 in The Lancetestimated that in India 200,000 people die annually from malaria, which is far more than previous estimates of around 15,000 per year. In addition, millions in India are sickened by the disease; of the 1.2 billion people in South Asia at risk of contracting malaria, most live in India.

The main focus of the Tulane project is to accelerate development of a vaccine that would interrupt transmission of the malaria parasite Plasmodium (P.) falciparum,which is responsible for the vast majority of malaria deaths. However, Kumar and his colleagues also plan to develop a vaccine construct for the corresponding 48/45 protein that is found in the P. vivax malaria parasite. Though considered not as severe and deadly as P. falciparumPvivax malaria is far more common in India and elsewhere outside of Africa. Approximately 40 percent of the world’s population is at risk of Pvivax infections, and MVI is committed to increasing support for vaccines targeting clinical disease caused by this parasite.

"We are excited to bring another transmission-blocking vaccine candidate into our portfolio and to do so by combining Tulane’s incredible team of malaria vaccine scientists with Gennova’s crucial ability to produce high-quality recombinant proteins," said MVI’s Loucq. "Eradicating malaria requires exceptionally creative thinking and truly global public- and private-sector partnerships and this collaboration has it all."

MVI is also supporting, with partners at the Johns Hopkins Bloomberg School of Public Health and the Sabin Vaccine Institute, development of a separate transmission-blocking vaccine that utilizes an antigen that appears to have the potential to block transmission of both P. falciparum and P. vivax.