The Race for a Malaria Vaccine

9th June 2010 (Last Updated August 9th, 2019 12:31)

Malaria is one of the most serious infectious diseases in the world. Accordingly, there is little surprise that major research is being undertaken to find a cure. Kenya McCullum caught up with the experts from one US military programme that holds technology that could provide an answer.

The Race for a Malaria Vaccine
Malaria is a disease with ancient origins that is the cause of much modern-day devastation – 500 to 600 million clinical cases, and nearly one million deaths, annually.

Malaria is a disease with ancient origins that is the cause of much modern-day devastation – 500 to 600 million clinical cases, and nearly one million deaths, annually. Although there are several malaria treatments currently available, the parasites that cause the disease are constantly mutating and becoming resistant to anti-malarial drugs.

To stop the devastation caused by the disease, the US military malaria vaccine programme, which consists of researchers from the army and navy, has teamed up with several companies in a race to create a malaria vaccine. We speak to Thomas Richie, director of the malaria programme at the Naval Medical Research Center, and George Siber, executive chairman of Genocea Biosciences, one of the military's industry partners, about the work they are doing to create a malaria vaccine.

Drugdevelopment.com: How important is it to develop a malaria vaccine?

Thomas Richie: Developing a malaria vaccine is one of the most important biomedical priorities facing us this century. Malaria is an ancient scourge of humankind and has caused more misery perhaps than any other single agent has throughout history – primarily in tropical and subtropical climates. It remains extremely important today because nearly all tropical countries have the possibility of malaria transmission.

DDT: What kinds of malaria treatments are currently available for patients?

TR: We actually have a number of different drugs for treating malaria. The most well-known is chloroquine, which was developed in the 1940s. It used to be a magic bullet for malaria. It killed all malaria parasites properly but the parasite has evolved resistance to chloroquine so in many parts of the world chloroquine is now a relatively ineffective drug. This pattern of developing resistance is something we've seen over and over again with anti-malarial drugs, so it's a good thing that we have a lot of drugs available because one by one they lose their power to treat infection successfully.

"Developing a malaria vaccine is one of the most important biomedical priorities facing us this century."

Most recently, a series of drugs have been developed that are based upon a Chinese herbal drug called artemisinin. There are several drugs in this class, and typically they are administered in combination with other drugs—which are called artemisinin combination treatments (ACTs).

To our horror, a significant resistance to ACT has emerged in Cambodia and the World Health Organisation is scrambling to organise a campaign to contain this strain of Plasmodium falciparum that is relatively resistant to ACTs.

DDT: What is lacking in the current malaria treatments?

TR: In terms of the drug treatment, right now we're in pretty good shape, but we're always desperately trying to identify new drugs as we know of this problem of resistance. Although we do have drugs currently, we could lose them, so we need to identify new drugs and there are a lot of different groups that are actually working on that.

DDT: How will a new vaccine combat these shortfalls?

TR: A vaccine is important because, like with any infectious disease, it's infinitely better to prevent it in the first place than to wait for someone to get sick and nearly die from it so that you can treat them. This is what makes vaccines by far the most cost-effective public health intervention. A vaccine would probably do more than any other single measure to control and eliminate malaria.

DDT: How did it come about that the Naval Medical Research Center and Genocea Biosciences partnered to create a malaria vaccine?

George Siber: Genocea has developed a new technology that will allow us to discover new antigens from the initial liver stage of the disease. Antigens are the key component of a vaccine that targets the immune response to destroying the Malaria parasites in the liver before they have a chance to spread to the bloodstream.

Genocea has the ability to determine which proteins, of the several thousand that Plasmodia make, are the targets of protective immunity. We will study subjects who are completely protected from malaria, such as volunteers at the Naval Medical Research Center, who have been challenged with live irradiated sporozoites.

DDT: What is the role of the other industry partners working with the US Military Malaria Vaccine Program to develop a vaccine?

TR: GlaxoSmithKline (GSK) is developing a vaccine, called RTS,S, which was originally developed as a partnership between the Walter Reed Army Institute of Research and GSK. RTS,S is currently being tested across Africa in a large Phase III study and this vaccine may be licensed for use in the sub-Saharan Africa in 2012.

"A series of malaria drugs have been developed that are based upon a Chinese herbal drug called artemisinin."

Another important collaboration is with GenVec, where we are developing vaccines that inject not the protein, but the DNA that encodes the protein. What's special about DNA-based vaccines, or genetic vaccines, is that they induce a different kind of immune response from protein-based vaccines.

Genetic vaccines induce primarily cell-mediated immunity and are a very potent way to attack the malaria parasite. We have recently tested this vaccine, called NMRC-M3V-D/Ad/PfCA, in a clinic and we have induced protective responses in about one quarter of our volunteers.

We are also developing whole organism vaccines with Sanaria Incorporated Seattle Biomed.

DDT: What is the process involved in creating a malaria vaccine?

GS: Genocea screens the protected patients and compares them with individuals that are not. We find the antigens associated with protection and evaluate them in animal models. Once we have confirmed protective activity, we formulate a vaccine using these antigens together with an appropriate adjuvant or delivery system designed to stimulate a b T-cell response, particularly CD8 T cells. Then we enter human clinical trials initially in adults (safety) followed by adults challenged with malaria (efficacy). If the vaccine seems to work, we would enter large field trials in children and babies in malaria endemic areas.

DDT: At what stage is the development of the malaria vaccine can you project when the vaccine will be available for patients?

GS: In April, we announced the agreement to develop the malaria vaccine with the Naval Medical Research Center. There are essentially two major steps to vaccine development: step one encompasses vaccine discovery and pre-clinical development, and step two includes clinical development.

Genocea has the greatest impact on the first step by reducing costs and time associated with antigen discovery and moving vaccine candidates into development that have a greater probability of success because the antigens were identified in naturally infected and protected humans. We just initiated the antigen discovery phase.

"With any infectious disease, it's infinitely better to prevent it in the first place than to wait for someone to get sick."

TR: The RTS,S won't be available to people in the US in the foreseeable future because it's not really sufficiently effective to prevent malaria in travellers. As a public health intervention in sub-Saharan Africa, it will hopefully save some lives and reduce some clinical illness, and it's hopefully going to be licensed in 2013.

As far as a better vaccine is concerned, we are targeting 2025. It's going to be a hard road to get greater than 90% protection, which is what we want.

DDT: What will be the overall effects of having a cure for malaria?

GS: Malaria is one of the most serious infectious diseases in the world, causing nearly a million deaths and hundreds of millions of clinical cases each year. It is a significant risk for American troops deployed to Asia, Africa, and other tropical and subtropical regions where malaria is endemic.

Having a safe and effective vaccine against malaria would be hugely beneficial to troops, travellers and immigrants returning from countries where malaria transmission occurs, as well as for populations living in endemic regions.