Vaccine Challenges

Why is developing a malaria vaccine difficult?

Many factors make malaria vaccine development difficult and challenging.

First, the size and genetic complexity of the parasite mean that each infection presents thousands of antigens to the human immune system. Understanding which of these can be a useful target for vaccine development has been complicated, and to date at least 40 promising antigens have been identified.

Second, the parasite changes through several life stages even while in the human host, presenting a different subset of molecules for the immune system to combat at each stage.

Third, the parasite has evolved a series of strategies that allow it to confuse, hide, and misdirect the human immune system.

Finally, it is possible to have multiple malaria infections of not only different species but also of different strains at the same time.

Is a malaria vaccine feasible?

Three specific findings point to the feasibility of developing a malaria vaccine.

The first is the infected sporozoite model in which irradiated sporozoites were delivered via mosquito bites to volunteers. When subsequently challenged with infected mosquitoes, the volunteers were protected.

The second is the gradual onset of natural protection from severe disease in humans living in malaria endemic areas and exposed to repeated infections.

The third is experiments that demonstrate the effectiveness of passive transfer of immunity. Together, these show that an immune response that protects from disease is possible. The challenge is to define those segments of the immune response that are required and the antigens that can generate a protective immune response, then develop ways to manufacture and safely present those antigens to the immune system.

Much of the malaria vaccine research going on around the world is focusing on methods of reproducing this immunity in a safe and effective way. Scientists are optimistic that an effective vaccine is indeed feasible. MVI is working to enhance and accelerate promising efforts, forging collaborations toward a safe and effective vaccine.

Read "Creating a Vaccine against Malaria" for more on malaria vaccine development.

…Getting to Market

Notes

Human volunteers can be completely protected against malaria infection by repeated injection with radiation-attenuated sporozoites.
The technique is highly impractical outside of research laboratories, but it provides a critical proof-of-concept and the knowledge that "sterile immunity" can be achieved. Volunteers immunized with this irradiated sporozoite vaccine are protected from different malaria strains (from the same species), and maintain their immunity for a relatively long time. More than two decades of research using this model have revealed important clues to the mechanisms of immunity, and have led to promising early results with at least one synthetically produced sporozoite vaccine candidate. (back)

Humans living under conditions of high malaria transmission develop clinical immunity to the disease. This immunity is species-specific, and wanes rapidly once a person leaves a malarious area.
After the age of about ten, people rarely develop severe clinical illness even though they may almost constantly harbor parasites in their blood (falciparum) or liver (vivax). Naturally acquired immunity, it seems, is due to a balance between the parasite and the host's immune system, which the host develops after repeated exposure to the parasite. (back)

Immune globulin purified from the blood of individuals who were life-long residents of malarious regions is highly effective against the blood stage form of the parasite.
This represents another reason for optimism. Malaria immune globulin has been used experimentally to successfully treat severe malaria infections in young children. This immune globulin contains antibodies that prevent the parasite from invading new red blood cells and dramatically increase their clearance by the spleen. In experimental animals, pretreatment with immune globulin prevents or dramatically blunts the force of a subsequent malaria challenge. Fear of transmitting other infectious diseases has stifled the further development of malaria immune globulin as a commercial product, but the experimental data again provide important information. (back)

Many antigens currently are being used in malaria vaccine development.
In the graphic below, antigens are listed according to the stage in which they would be expected to provoke a protective immune response. MVI is developing partnerships to accelerate the development of select vaccines in each category.

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