Live Vaccines Against Malaria

For a long time, malaria is one of the most serious diseases threatening human health. According to the WHO, there were 229 million clinical cases of malaria worldwide in 2019, and more than 400,000 people died from this disease. Although some countries have been confirmed by the WHO to eliminate malaria, which is still raging in regions such as Africa and South America. For more than ten years, the use of antimalarial drugs (such as artemisinin) and the elimination of Anopheles (malaria vectors) have achieved remarkable results in eradicating malaria, but there are also barriers in the way to complete eradication. Vaccines are an important means to eliminate infectious diseases. Since Plasmodium Parasites was identified as a pathogen of malaria more than a hundred years ago, the academic community has been working hard to develop a highly effective vaccine against malaria infection. However, no anti-malarial vaccine has been put on the market so far. The challenge of R&D comes from the complex pathogen genome (more than 5,300 genes) and the complex life cycle (blood-liver-blood). In order to overcome these challenges, Agnes Mwakingwe-Omari of the GlaxoSmithKline Vaccine Research Center in Rockville, Maryland, USA, reported the use of complete live Plasmodium falciparum as a vaccine, supplemented by a new vaccination strategy controlled by chemical drugs (pyrimethamine and chloroquine). Related research results were published in Nature entitled "Two chemoattenuated PfSPZ malaria vaccines induce sterile hepatic immunity". Their live vaccine (https://www.creative-biolabs.com/vaccine/live-attenuated-and-killed-vaccine-design.htm) strategy is based on the life cycle of the malaria pathogen—Plasmodium in the human body. The malaria parasite enters the blood through the bite of Anopheles mosquitoes and transfers to the liver in the form of sporozoites to proliferate in the liver cell vacuoles. No symptoms appear at this moment, and then the malaria parasite returns to the bloodstream, invading red blood cells and causing disease symptoms. Sporozoites and liver stage parasites, also known as pre-erythrocyte stage (PE) parasites, are important targets for vaccine R&D. Previous studies have used the radiation-attenuated live vaccination (Pf SPZ-RAS) strategy. After vaccination, the vaccine cannot proliferate in the liver, and the protection against malaria is weak. Mwakingwe-Omari et al. chose complete live parasites as vaccines, supplemented by drug treatment to kill parasites in a specific period of their life cycle to achieve the immune effect, for which they carried out a series of clinical experiments that elucidated that antibodies from liver-resident parasites are essential for inducing long-lasting anti-malarial immunity beyond strain. In addition, they observed that the protective effect of pyrimethamine is not as good as that of chloroquine, implying that in vaccine development, the intact hepatic development of the parasite can be maintained without entering the blood infection phase, so as to further enhance the immune response. There are still many problems that need to be solved for the method of live vaccination supplemented by drugs to move towards clinical application: 1. The patients need to be vaccinated three times and take antimalarial drugs in strict accordance with regulations in the later stage. Such strict control conditions are difficult to implement among billions of people. Future research also needs to detoxify live vaccines instead of drug control.rn2. There are technical challenges in the large-scale production of live vaccines.rn3. Future research needs to determine which antigens of pre-erythrocytic vaccines are recognized by CD8 T cells in order to develop personalized antigen vaccines (https://www.creative-biolabs.com/vaccine/antigen-vaccines.htm).