Halting the World’s Most Lethal Parasite

Tempo di lettura: 4 min

New ideas for a malaria vaccine have been developed, and hopefully a new solution is going to come out in the next 4 – 5 years. The most important ones are:

 

            1) GSK’s (GlaxoSmithKline) scientist Joe Cohen, with a project called RTS,S. He says:”If all goes well, five years from today, a vaccine could start being implemented in a wide way in six- to 12-week-old children.” Cohen started working in the mid- 1980s with a protein called Plasmodium falciparum, contained in the surface of the malaria parasite. This parasite is contained in the mosquito’s salivary glands, moves to the human bloodstream, then into human liver, where it develops until completely grown up, comes back to human bloodstream and moves back into a new mosquito. Since that first release of RTS,S, scientists at GSK kept reinventing the candidate, until they found something that has reached late-stage human trials. This trial of the vaccine has been proven safe and is now being tested at 11 sites in Africa, where the risk of malaria is higher. In the last version of RTS,S a new protein called CShas been added, (circumsporozoite) that works as an antigen.

It provokes the immune system to create antibodies that attempt to kill the parasite before it reaches the full-grown stadium. However, the immune system didn’t react as planned; the scientists had to reformulate the vaccine to provoke a strong-enough reaction. After 15 years they finally succeded adding a chemical that increased the number of antibodies produced, creating B cells.

Still, there are several hurdles: the first one is the cost. The development of RTS,S and its production will cost millions of dollars, but GSK hopes that associations such as UNICEF and The Global Alliance for Vaccines and Immunization will buy it and distribute it in the highest risk zones.

The second one is the percentage of working; it’s extremely difficult that RTS,S will have a percentage higher than 80 before it is approved for wide use. Now it is effective in 50 % of cases. That means that it would never be used just by itself to completely wipe out malaria form an organism.

The third problem is that RTS,S is working with the African strain of Plasmodium falciparum, not the other strains that are present around the world.

           

            2) Scientist Rhoel Dinglasan has another theory to defeat malaria: he and his team of researchers cultured weakened parasites in lab and put them into the body of mosquitos. Substantially, Dinglasan’s goal is to immunize mosquitos from the parasite, preventing in this way, the spread of malaria.

When the parasite enters a mosquito’s body, it looks for an aminopeptidase (an enzyme) in the gut. It must find it within 24 hours, otherwise the parasite will get digested and the mosquito will not be infected. Dinglasan wants to treat mosquitos with antibodies against the aminopeptidase, giving them protection against malaria.

The theory is that the antibodies mask the enzyme, preventig the parasite to target it.

Mosquitos pick up those antibodies by biting someone or something that already has them, (Dinglasan treated mice with those antibodies and made them been bitten by mosquitos, making them pick up the antibodies).

But there’s a problem: the vaccine protects mosquitos, not people. In this case a person could get malaria even if vaccinated, becaues bitten by a mosquito that picked up malaria by someone who was not immunized. Dinglasan has also done tests with the Plasmodium vivax, other than the Plasmodium falciparum, showing 100 % of success in tests on mice.

 

            3) Stefan Kappe’s of SeattleBioMed theory and Stephen Hoffman’s, chief of Sanaria, was originally discovered in the 1970s by the U.S. Navy: they found out that if you are bitten by some weak-parasite carriers mosquitos. In this case the parasite won’t be strong enough to develop into its adult form; meanwhile the body will notice the pathogen agent and create antibodies against it, being immunized from malaria.

This operation was originally successful only in 50 % of the cases, but now Kappe and Hoffman are creating weakened parasites extracted from the mosquitos’ salivary glands to see if this solution may be suitable for a vaccine.

They have two ways to treat the parasite: in the first one, to weaken it, scientists take out two genes from the parasite, which makes it build a membrane around itself while taking place in the human liver. The development of the membrane is very useful, because prevents the liver from realizing they are infected. Parasites without membrane cause a liver cell failure instead of hosting it and allowing it to grow up. SeattleBioMed has found that this process is 100 % successful, and doesn’t cause any kind of problem with the liver.

This spring this process had been tested on 20 people and we’ll see the results in the next months. If they find malaria’s parasites in their bloodstream, they will be treated with anti-malarial medications.

The other way to wreck a malaria parasite is to irradiate it. Hoffman’s biotech company says that it may have advantages.

The radiations “confuse” the genetic code in more sites than two, ensuring in this way, that the parasite grows up once in the liver. Because this is just an empirical attempt, Hoffman’s first try was half a failure: he and his team thought that a mosquito injects between 5 and 10 parasites, therefore they based the strength of the dose on that recording. They discovered later that a mosquito  actually injects between 300 and 500 parasites; in this way the too-low doses provided some protection against malaria, but they weren’t as effective as RTS,S. Now Hoffman has increased the concentration of parasites and hopefully he will get a higher percentage of success with this procedure.

 

Filippo Albertino (4D)

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