May 30, 2017Tropical Medicine
Malaria is a mosquito-borne infectious disease affecting humans and other animals caused by parasitic protozoans (a group of single-celled microorganisms) belonging to the Plasmodium type. Malaria causes symptoms that typically include fever, feeling tired, vomiting, and headaches. In severe cases it can cause yellow skin, seizures, coma, or death. Symptoms usually begin ten to fifteen days after being bitten. If not properly treated, people may have recurrences of the disease months later. In those who have recently survived an infection, reinfection usually causes milder symptoms. This partial resistance disappears over months to years if the person has no continuing exposure to malaria. The disease is most commonly transmitted by an infected female Anopheles mosquito. The mosquito bite introduces the parasites from the mosquito's saliva into a person's blood. The parasites travel to the liver where they mature and reproduce. Five species of Plasmodium can infect and be spread by humans. Most deaths are caused by P. falciparum because P. vivax, P. ovale, and P. malariae generally cause a milder form of disease.
Malaria symptoms occur when the plamodium parasite replicates inside red blood cells and cause them to burst. To enter blood cells, the parasite first secretes its own receptor protein, RON2, onto the cell's surface. Another parasite surface protein, AMA1, then binds to a specific portion of RON2, called RON2L, and the resulting complex initiates attachment to the outer membrane of the red blood cell. Several experimental malaria vaccines previously tested in people were designed to elicit antibodies against AMA1 and thus prevent parasites from entering blood cells. Although AMA1 vaccines did generate high levels of antibodies in humans, they have shown limited efficacy in field trials in malaria-endemic settings.
According to an article published on line in the journal npj Vaccines (22 May 2017), a modified experimental malaria vaccine showed that it that it was able to completely protect four of eight monkeys who received it against challenge with the virulent Plasmodium falciparum malaria parasite. In three of the remaining four monkeys, the vaccine delayed the time when parasites first appeared in the blood, by more than 25 days. To improve vaccine efficacy, the authors modified an AMA1 vaccine to include RON2L so that it more closely mimics the protein complex used by the parasite. Monkeys were vaccinated with either AMA1 alone or with the AMA1-RON2L complex vaccine. Although the overall levels of antibodies generated did not differ between the two groups, animals vaccinated with the complex vaccine produced much more neutralizing antibody, indicating a better quality antibody response with AMA1-RON2L vaccination. Moreover, antibodies taken from AMA1-RON2L-vaccinated monkeys neutralized parasite strains that differed from those used to create the vaccine. This suggests, the authors noted, that an AMA1-RON2L complex vaccine could protect against multiple parasite strains. The authors then concluded that taken together, the data from this study justify progression of this next-generation AMA1 vaccine toward possible human trials.