Why is the malaria vaccination losing its protective effect so quickly – Genetics News

Scientists from the German Center for Cancer Research (DKFZ) studied the human immune response after immunization with the malaria pathogen Plasmodium falciparum. Their goal was to find out which protein components of the T helper cells are stimulated. To the researchers’ surprise, the helper T cells interacted exclusively with the protein sequence of the vaccine strain and showed no cross-reactivity with naturally occurring pathogenic variants. This could explain why natural infection, to which residents of endemic areas are constantly exposed, provides little protection against new diseases of other strains, and why the effect of vaccination available so far only lasts for a short time.

Despite impressive successes in combating malaria, more than 600,000 people worldwide still die each year from this 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 effectiveness, already low, does not last long.

The vaccine is directed against CSP, which is the quantitatively dominant protein on the surface of ‘sporozoites’. Sporozoites are a stage of malaria that is transmitted by mosquito bites and enters human blood. To improve a vaccine, we need to understand which protective antibodies are stimulated by immunization. But the production of such antibodies largely depends on the help of the so-called follicular helper T cells, ”explains Hedda Wardmann of the German Cancer Research Center. They ensure that B cells turn into antibody-producing plasma cells and memory B cells.”

To study the helper T-cell response against CSP in detail, the team led by immunologist DKFZ Wardemann examined the blood of volunteers infected with P. falciparum sporozoites from the vaccine strain. The volunteers were of European origin and had no previous contact with the malaria pathogen. The researchers analyzed the follicular helper T cells of Plasmodium at the single-cell level. In particular, they focused their research on CSP sequences that are recognized by T helper cell receptors.

Analyzes revealed that T-cell receptors primarily target amino acids 311-333 of CSP. But another observation astonished the researchers: there was almost no cross-reactivity between individual T-cell clones. “Even deviations of a single amino acid component were not tolerated in some cases,” Wardman says.

The immunologist indicates that sequence polymorphisms occur to a high degree in this region of the CSP in natural populations of P. falciparum. “The specificity of the T-cell cloning prevents the constantly recurring natural infection by the pathogen from acting as a natural ‘booster’. This may explain why the protective effect of the malaria vaccine wears off so quickly. The researcher recommends additional testing for vaccine development to see if induction of a broader spectrum of T cells would be effective. Help can generate long-term immune protection.

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Material provided by German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ). Note: Content can be modified according to style and length.

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