.

Technological Landscapes: Therapeutic Vaccines Target Malaria

Lexington-based Agenus Inc., a biotechnology company that develops therapeutic vaccines for cancer and infectious diseases is a major contributor to the war on malaria.

 

The World Health Organization (WHO) estimates that in 2010 malaria caused 655,000 deaths worldwide. Most of the deaths were among African children, especially in sub-Saharan Africa, where just about every minute a child dies from the disease. Annually, there are over 200 million cases of malaria. The disease is spread by parasites transmitted to people through the bites of infected mosquitoes. The use of drugs to prevent the disease has become problematic due to evolutionary drug-resistant-strains developed in both the parasite and the mosquito population.

Although there is currently no licensed vaccine against malaria, the concept of a therapeutic vaccine for malaria is thought to be worth an extensive effort. It is for this reason that the “WHO Global Malaria Program” was established. The dynamic effort is being led by a consortium that includes GlaxoSmithKline Biologicals, a world leader in vaccine technology; the PATH Malaria Vaccine Initiative, a global program established via an initial grant from the Bill & Melinda Gates Foundation; and Lexington-based Agenus, a biotechnology company that creates therapeutic vaccines for infectious diseases.

The scope of the effort is extraordinary. In 2007, Melinda Gates set the audacious goal to completely eradicate malaria. The Gates foundation has committed $750 million to its global fund to battle AIDS, Tuberculosis and Malaria.

Since 1999, at least $600 million has been spent by numerous malaria vaccine research groups that are part of this ambitious effort. The goal is to produce a first generation vaccine by 2015 that offers at least 50 percent protection in infants and children and lasts a minimum of one year. The most promising malaria vaccine to-date is called “RTS,S”, manufactured by GlaxoSmithKline.

The New England Journal of Medicine has reported that clinical Phase 3 trials, concluded in November of 2011, have demonstrated positive results in a study of six-thousand African children. Follow-up testing results are expected by year’s end, 2012.

The Agenus QS-21 Stimulon adjuvant is a key component of the RTS,S malaria vaccine. An adjuvant is a substance added to a vaccine to enhance its therapeutic impact. The adjuvant stimulates the immune system’s response to the malarial infection but does not in itself cause immunity. Although the use of adjuvants is common, the concept is not widely referred to or generally understood. For example, the adjuvant ALUM, an aluminum salt, is a component of licensed human vaccines which protect against such diseases as diphtheria, tetanus, rabies, hepatitis, influenza and anthrax.

In the case of QS-21, Agenus fact sheets indicate that the adjuvant is a saponin extracted from the bark of the Quillaja saponaria tree, also known as the soap bark tree or Soapbark. It is an evergreen tree native to warm, temperate central Chile. Quillaja raw material has been used for decades as an ingredient to create the foaming in beverages such as root beer and other carbonated beverages. It has also been used as an adjuvant in veterinary vaccines.

The term “saponin” is also unfamiliar. It is a complex organic chemical compound found abundantly in various plant species. The saponins are commonly used in products that form a part of the lucrative dietary supplement industry.

The Agenus QS-21 adjuvant is not a sudden development. Since its intensive use in early 2000 many thousands of patients during hundreds of clinical trials have received vaccines containing QS-21 with effective results. Such results have raised the hope that its use in the RTS,S vaccine will prove to be effective.

Success in the eradication of malaria comes in small steps. The November 2011 clinical trial indicated a 55% reduction in malaria cases for children five to seventeen months old during a twelve month period. This result, although limited, was considered a major breakthrough by the consortium. They were encouraged to continue and the current testing phase involves eleven trial sites in seven African countries.

Those involved in the process believe that it is better to have even a partially effective vaccine than none because it is difficult to get healthcare to so many rural areas. In contrast, delivering the vaccines to even the remotest parts of Africa is within the capability of the healthcare workers.

The RTS,S malaria vaccine is only part of the total cure. Bed nets, spraying and well-equipped treatment facilities for children and adults who do contract the disease are still required. Clearly, until there can be a 100 percent effective malaria vaccine, the present drug treatments are still required and considerable funding is needed to keep ahead of the natural development of drug-resistant strains.

Agenus, with its development of the QS-21 adjutant, is a vital contributor in this war on malaria.

Boards

More »
Got a question? Something on your mind? Talk to your community, directly.
Note Article
Just a short thought to get the word out quickly about anything in your neighborhood.
Share something with your neighbors.What's on your mind?What's on your mind?Make an announcement, speak your mind, or sell somethingPost something