The search for a safe, effective vaccine to protect billions of at-risk people from malaria continues, and the newest study from the German Cancer Research Center (DKFZ) has the latest discovery: a potential basis for a new vaccine built on amino acid sequences of proteins found on the Plasmodium parasite, the pathogens responsible for malaria.
"Ideally, a vaccine should elicit an antibody response against the so-called sporozoites, the parasite stage that the mosquito transfers to humans," explained DKFZ’s Hedda Wardemann. "If the immune system is able to destroy the infectious agent at this stage, before it reaches the liver, then the infection is stifled from the start."
This was the approach taken by Wardemann and other scientists in the new study, published in the journal Immunity. After being bit by a mosquito carrying Plasmodium, the parasite enters the host in the form of sporozoites, which in turn infect liver cells where they mature and multiply. After leaving the liver, the parasites are now in the form of merozoites, which invade red blood cells and grow exponentially. As red blood cells are infected and killed, typical malaria symptoms occur.
Researchers collected blood samples from people living in a high-risk area for malaria, to examine how the immune system forms memory B cells in response to an infection. Memory B cells are typically formed alongside antibody-producing B cells during an infection, but they hold onto their antibodies instead of releasing them into the bloodstream, that is until the pathogen appears again. If it does, the immune system is already armed with the right antibodies to launch an attack.
After isolating memory B cells with antibodies targeting Plasmodium sporozoites, researchers saw that there were not very many memory cells, but that was expected. Only a handful of sporozoites make it into the blood with every mosquito bite, and those that do disappear almost immediately in the liver. "The quantity is simply too small to stimulate the immune system sufficiently," Wardemann said.
However, for the few memory B cells the researchers did find, the antibodies they produced were able to protect mice from infection by sporozoites. Using the exact amino acid sequences of the sporozoite protein targeted by the antibodies, researchers build a new basis for a malaria vaccine.
"An effective vaccine must cause the memory cells to generate an extremely powerful response - before the sporozoites disappear out of reach into the liver,” Wardemann explained. “To make this happen, we must know the targets of a protective immune response as exactly as possible.”
Source: German Cancer Research Center
