22 June 2021

RNA vs plasmodium

mRNA malaria vaccine showed 88 percent efficacy in mice

Anastasia Kuznetsova, N+1

American scientists have created a malaria vaccine based on modified matrix RNA. Studies on mice have shown 88 percent effectiveness with triple immunization with an interval of nine weeks. Despite the good results in animals, the vaccine has yet to be confirmed to be highly effective in humans, which malaria vaccines do not always succeed. The work was published in npj Vaccines (Mallory et al., Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice).

Malaria is caused by unicellular organisms of the genus Plasmodium. The most common disease occurs after a mosquito bite infected with Plasmodium falciparum. In 2018, 228 million people worldwide were infected with malaria, and 405 thousand people died. Most of the vaccines created before that turned out to be ineffective against malaria. At the moment, the only RTS,S vaccine has been approved for use. Its effectiveness is 30-50 percent, depending on the age group, and four doses are needed for full immunization. The vaccine developed by Sanaria showed 90 percent effectiveness in tests on a small sample, but after the second phase of clinical trials, the effectiveness was at the level of 77 percent.

Scientists led by Evelina Angov from the Walter Reed Army Research Institute decided to create a vaccine against malaria based on mRNA. It uses the mRNA of one of the Plasmodium falciparum membrane proteins enclosed in a lipid nanoparticle to create immunity. This design prevents premature degradation of the nucleic acid. Cells synthesize a protein with mRNA, which generates an immune response with the production of antibodies.

To create the vaccine, scientists used mRNA from two sources – one from TriLink, and the other from University of Pennsylvania (UPenn). The regions encoding the viral protein were identical in them, but in UPenn mRNA, non-coding regions were optimized to improve protein synthesis. The researchers divided the mice into groups of 10 animals. They were immunized three times with an interval of three weeks, and two weeks later they were infected with malaria plasmodium. The same experiment was carried out, increasing the interval between doses to 6 weeks.

With an immunization regimen with a three-week break between doses, vaccines based on different mRNAs showed the same effectiveness (40 percent), and in the group of animals that received doses with an interval of 6 weeks, the vaccine based on modified mRNA (UPenn) showed higher efficacy (88 percent) compared to unmodified mRNA (65 percent).

Despite the encouraging results obtained in animals, it is too early to talk about success in the development of a vaccine, since malaria vaccines often prove less effective in clinical trials. At the same time, the design of a new mRNA-based vaccine makes it possible to modify the sequence so as to improve its stability and immunogenicity. This is what further research will be aimed at.

Malaria can be contracted not only in African countries. In the early 2000s, there was an outbreak of malaria in the Moscow region, which was brought by immigrants from Tajikistan. Plasmodia had only a few hot weeks to mature in Moscow mosquitoes.

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