The German Cancer Research Center investigated the human immune response to the malaria parasite Plasmodium falciparum vaccination. Their results might explain why natural illnesses, to which individuals in endemic regions are repeatedly exposed, provide little protection against new diseases with various strains, and why the efficacy of current vaccinations is only temporary.
Despite great gains in malaria management, the World Health Organization estimates that more than 600,000 people die from the tropical illness each year. The pathogen Plasmodium falciparum is responsible for the great majority of fatal cases of malaria. There is now just one authorised vaccination against this single-celled organism, and its efficiency, which is already rather poor, is short-lived.
CSP, the quantitatively dominating protein on the surface of “sporozoites,” is the target of the vaccination. Sporozoites are the stage of the malaria infection that enters human blood after being transmitted via mosquito bite.
“To develop the vaccine, we must first determine which protective antibodies are stimulated by inoculation. However, the generation of such antibodies is heavily reliant on the assistance of so-called follicular T helper cells “Hedda Wardemann of the German Cancer Research Center concurs. “They make certain that B cells differentiate into antibody-producing plasma cells and memory B cells.”
The team lead by DKFZ immunologist Wardemann studied the blood of volunteers infected with deceased P. falciparum sporozoites from the vaccine strain to explore the T helper cell response to CSP in depth. The subjects were of European ancestry and had no previous exposure to malaria infections.
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The researchers examined single cells of generated Plasmodium-specific follicular T helper cells. They concentrated their research on which CSP sequences are recognised by T helper cell receptors in particular.
The findings indicated that T-cell receptors mostly targeted CSP amino acids 311 to 333. Another finding astounded the researchers: there was almost little cross-reactivity between the various T-cell clones.
“The receptors bind only the CSP epitopes of the vaccination strain in question. In several circumstances, variations of only one amino acid component were not permitted “Wardemann elaborates.
The immunologist points out that sequence variations in this area of the CSP are common in the wild population of P. falciparum.
“The specificity of the T-cell clones precludes naturally recurrent pathogen infections from functioning as a natural ‘booster.’ This might explain why the malaria vaccine’s protective effect wears off so soon “Wardemann explained. The researcher suggests that future vaccine development should investigate whether activating a broader range of T helper cells might result in longer-lasting immune protection.
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