Updated: June 21, 2022 22:51 IST
Washington [US], Jun 21 (ANI): Scientists at the German Cancer Research Center have studied the human immune response after immunization with the malaria pathogen Plasmodium falciparum. Their findings could explain why natural infections, to which people in endemic areas are constantly exposed, offer little protection against new diseases with other strains, and why the effect of the available vaccinations is short-lived.
Despite impressive success in fighting malaria, more than 600,000 people worldwide still die each year from the tropical disease, according to the World Health Organization. The vast majority of fatal malaria cases are caused by the pathogen Plasmodium falciparum. To date, there is only one approved vaccine against this single-celled organism and its efficacy, which is already quite low, does not last long.
The vaccine targets CSP, the quantitatively dominant protein on the surface of the ‘sporozoites’. Sporozoites are the stage of the malaria pathogen that is transmitted with the bite of the mosquito and enters the human blood. “In order to improve the vaccine, we need to understand which protective antibodies are induced by the immunization. But the production of such antibodies largely depends on the help of the so-called follicular T helper cells,” says Hedda Wardemann of the German Cancer Center Research Center . “They cause B cells to transform into antibody-producing plasma cells and memory B cells.”
To study the T helper cell response to CSP in detail, the team led by DKFZ immunologist Wardemann examined the blood of volunteers infected with killed P. falciparum sporozoites from the vaccine strain. The volunteers were of European descent and had never been in contact with malaria pathogens before. The researchers analyzed the induced Plasmodium-specific follicular T helper cells at the single-cell level. In particular, they focused their research on which sequences of CSP are recognized by the receptors of the T helper cells.
The analyzes showed that the T cell receptors mainly targeted amino acids 311 to 333 of the CSP. But another observation surprised the researchers: there was virtually no cross-reactivity between the individual T-cell clones. “The receptors very specifically bind only the CSP epitopes of the vaccine strain used. Even deviations of only a single amino acid component were not tolerated in some cases,” explains Wardemann.
The immunologist points out that in the natural population of P. falciparum sequence polymorphisms are highly prevalent in this region of the CSP. “The specificity of the T-cell clones prevents the constantly recurring natural infections with the pathogen from acting as a natural ‘booster’. This could possibly explain why the protective effect of the malaria vaccine disappears so quickly,” Wardemann said. The researcher recommends that further vaccine development should test whether inducing a broader spectrum of T helper cells could generate longer-lasting immune protection. (ANI)