Seattle BioMed researchers today announced they have developed a next generation genetically attenuated parasite (GAP) that might constitute the path to a highly protective malaria vaccine. The study was published online in the journal Molecular Therapy.
Malaria is caused by Plasmodium parasites that are transmitted to humans by a mosquito bite, leading to 219 million documented cases and 627,000 deaths worldwide in 2012. While control measures, such as bed nets, are increasingly implemented, there remains no effective vaccine capable of eradicating malaria.
The manuscript describes the development of genetically engineered malaria parasites that are weakened by the precise removal of genes and designed to effectively prevent the parasite from inducing an infection in humans. These genetically attenuated parasites, or "GAPs," are incapable of multiplying, but are alive and able to effectively stimulate the immune system to build up defenses to prevent pathogenic infection. While this vaccine strategy has proven very successful in providing protection against viruses and bacteria, it remains a novel approach in combating parasites.
"While vaccination with live-attenuated parasites is capable of providing complete protection from malaria infection, it is imperative that we permanently cripple the very complex malaria parasite so that it cannot cause disease, and instead, effectively primes the immune system," said Stefan Kappe, Ph.D., corresponding author and professor, Seattle BioMed.
"This most recent publication builds on our previous work," said Sebastian Mikolajczak, PhD., Seattle BioMed senior scientist and GAP project leader. "The first generation GAP strain had two genes removed from the malaria parasite, but this new 'triple punch', developed in collaboration with scientists at the Walter and Eliza Hall Institute in Australia, removes three separate genes associated with the pathogenicity of the parasite, effectively abrogating its ability to establish an infection in humans."
"The next step is to test the safety and efficacy of this attenuated parasite in clinical trials in a highly efficient manner," said Alan Aderem, Ph.D., president, Seattle BioMed. "Seattle BioMed's Malaria Clinical Trials Center is one of only four centers in the world approved to safely and effectively test new malaria treatments and vaccines in humans by the malaria human challenge model. We are committed better understanding and eventually eradicate this deadly pathogen."
The above story is based on materials provided by Seattle Biomedical Research Institute (Seattle BioMed). Note: Materials may be edited for content and length.
- Sebastian A. Mikolajczak, Viswanathan Lakshmanan, Matthew Fishbaugher, Nelly Camargo, Anke Harupa, Alexis Kaushansky, Alyse N. Douglass, Michael Baldwin, Julie Healer, Matthew O’Neill, Thuan Phuong, Alan Cowman, Stefan H.I. Kappe. A next generation genetically attenuated Plasmodium falciparum parasite created by triple gene deletion. Molecular Therapy, 2014; DOI: 10.1038/mt.2014.85
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