Malaria vaccine in the pipeline

Jul 29 2009

Australian scientists have developed the first genetically-engineered malaria vaccine and the vaccine will be trialled in humans early next year.

Using funds from the Bill & Melinda Gates Foundation a team led by Professor Alan Cowman from the Walter and Eliza Hall Institute in Melbourne, have created a weakened strain of the malaria parasite that will be used as a live vaccine against the disease.

The vaccine was developed in collaboration with researchers from the U.S., Japan and Canada and Professor Cowman, who is head of the Institute's Infection and Immunity division, says in developing the vaccine they had deleted two key genes in the Plasmodium falciparum parasite - which causes the form of malaria most deadly to humans.

Professor Cowman says by removing the genes, the malaria parasite is halted during its liver infection phase, preventing it from spreading to the blood stream where it can cause severe disease and death.

Malaria kills more than one million people each year and destroys - through premature death and disability - the equivalent of at least 35 million years of healthy, productive human life every year.

According to Professor Cowman, similar vaccines had been tested in mice and offered 100% protection against malaria infection and hopefully the vaccine would produce similar results in humans.

Professor Cowman says although the two genes have been deleted the parasite is still alive and able to stimulate the body's protective immune system to recognize and destroy incoming mosquito-transmitted deadly parasites.

This approach to vaccine development, by using a weakened form of the whole organism that causes a particular disease, has proven successful in eradicating smallpox and controlling diseases such as flu and polio and Professor Cowman says in developing the vaccine the team used knowledge from decades ago that irradiated malaria parasites provide protection against subsequent malaria infection in animal models and humans.

Professor Cowman says although vaccines are under development that use whole malaria parasites weakened by irradiation to protect against infection, their safety and effectiveness rely on a precise irradiation dose and trial results have been variable and they believe their genetically attenuated parasite approach provides a safe and reproducible way of developing a whole organism malaria vaccine.

Professor Cowman says it was unlikely the weakened parasites used in the vaccine would regain their potency as the genes had been deleted from the genome and could not be recreated by the parasite - also the 'one-two punch' approach of deleting two essential genes make it extremely unlikely that the attenuated parasite vaccine could restore its capacity to multiply and lead to disease.

The human trials of the vaccine will take place at the Walter Reed Army Institute of Research in Maryland, US - the genetically attenuated parasites to be used in the trial are being manufactured at the Walter and Eliza Hall Institute, which has the only facility worldwide capable of producing genetically-altered malaria parasites that comply with the good manufacturing practice guidelines required for human clinical trials.

The research team includes Dr. Matthew O'Neill and Dr. Alex Maier from the Institute as well as scientists from the Seattle Biomedical Research Institute, the Walter Reed Army Institute for Research and the University of Maryland.

The research is supported by a U.S.$17 million, five-year grant from the Bill & Melinda Gates Foundation and is published in the current issue of the Proceedings of the National Academy of Sciences USA.