Innovative malaria vaccine

Innovative malaria vaccine from the genetically edited live parasite

For this reason, in addition to focusing on the preventive measures of the disease, as is the eradication of vector-creation sites (mosquitos) and avoiding contact with them, researchers have also focused for years on the design of vaccines to cope with this health problem, but when being a parasite that crosses different stages in their life cycle has been delayed a long time.

Only one year ago, in 2021; the first vaccine was approved only in severe and potentially fatal cases in children, with an effectiveness of 36%, leaving adults and other children still unprotected. Its name is RTS,S/AS01 and is developed by the pharmaceutical company GlaxoSmithKline (GSK). This is a recombinant vaccine, i.e. it contains two merged proteins: a proteinP. falciparum antigenic along with hepatitis B virus surface antigen (which also provides HB protection).

It acts by generating antibodies in the organism that prevent the proliferation of parasites in the liver and ende, protect the patient from spreading to the bloodstream and attack on their red blood cells. The problem is that it covers only one part of the population (children) and a percentage of reduced efficiency, in addition to that several doses should be applied to be effective: three between the five and nine months of age, and one quarter to the two years. This is why the project of other experimental malaria vaccines in the first phases of clinical development continues to be advanced.

Most of them have as white several of the antigens considered important in triggering an effective immune response. Until 1 week ago, creativity and effectiveness in a new candidate vaccine seemed very distant. However, a research group managed to eliminate 3 parasite genes that make it aggressive and inject it live directly in patients to generate immunity. This group belongs to the University of Washington together with the National Institute of Infectious Allergies and Diseases and the Seattle Children's Research Institute and published in Science the drawing of this Plasmodium falciparum genetically modified that can be used as an even more effective vaccine than those designed so far.

To explain your method of action first one must know how the life cycle of this parasite, which crosses different stages of development: Female Anopheles mosquito when feeding of blood inocculates phase Spoorozoits in the human host. There, the liver cells (hepatocytes) are infected and the parasite crosses the steps of schizontes and merozos. These last infect the red blood cells where the parasite multiplies by asexual and crosses the stadium Trophozoites. Some of them differ goocytes (males and females) which are ingested by the mosquito where they make sexual reproduction giving rise to Spoorozoits where the cycle begins again.

To achieve its design, this group uses the type of attenuated vaccines in a very particular way: genetically modifies the sporozoite stage P. falciparum and uses it alive as an inducer of the immune system, thus avoiding the initial infection of the parasite in the liver. These genetically attenuated parasites do not require irradiation attenuation or concomitant pharmacological treatment. This genetic edition consists of the deletion of the genes P52, P36 and SAP1, which are related to correct replication within infected hepatocytes and give it the name PfGAP3KO "Plasmodium falciparum genetically attenuated parasite with three knockouts".

In the investigation of the Washington team, the vaccine was administered three or five times for about 200 bites for each immunization of mosquitoes infected with genetically edited sporozoites (with the 3 deletions), without causing any infection in the bloodstream of the patients. The adverse events related to the vaccine were unique and logically localized urticaria related to the numerous bites of mosquitoes administered by each vaccination (200). In addition, one month after final immunization through bites of mosquitoes infected with P. falciparum, It was observed that half of the people of each vaccinated group were resistant and immune to P. falciparum, and a subset of these people was submitted to a second study 6 months later remaining partially protected.

Therefore, maybe this vaccine can replace the first one that was approved by the WHO in 2021, because it has a higher percentage of effectiveness and can cover and immunize more population groups.

In addition, vaccines have not yet been developed against most parasites, such as Trypanosoma cruzi cause of Chagas evil, a local regional health problem disease in Argentina and in many Latin American countries transmitted by the chinche de chagas. Therefore, this discovery could be the beginning of a shift of course in the projects of parasite vaccines, from seeking antigenic target molecules to activate immune systems, to genetically edit certain parasite stages as possible vaccines, saving millions of people.