Study Explains Why Malaria Vaccine Loses Its Protective Effect Quickly

Scientists from Germany probing immune response in humans following inoculation with the malaria parasite Plasmodium falciparum have found a possible explanation for why the effect of the malaria vaccine doesn’t last.

Malaria Mosquito

Malaria Mosquito

The team of researchers from the German Cancer Research Center (DKFZ) surprisingly found that follicular T helper cells react solely to the malaria vaccine strain’s protein sequence. The cells showed practically no cross-reactivity with the natural population of the malaria pathogen.

Read Also: Scientists Discover a Way to Halt Malaria Parasite Development at an Early Stage

This finding may explain why vaccination’s effect does not last long, the researchers said.

The German scientists, led by DKFZ immunologist Hedda Wardemann, published their findings in the journal Science Immunology.

Protecting against malaria

Significant improvements have been made in the control of malaria globally over the past decades. However, the World Health Organization (WHO) reports that more than 600,000 malarial deaths are still recorded each year. The pathogen P. falciparum is responsible for most of these fatal cases.

Vaccination has been considered an option for protecting more effectively against malaria pathogens. But there has only been one vaccine approved for this purpose.

The vaccine is targeted against CSP, the most abundant protein on the outside of the “sporozoites.” The infective stage of the malaria parasite – when it is transmitted into human blood – is called sporozoites.

However, the efficacy of this vaccine is poor and, more worryingly, does not hold up for long. Scientists say knowing what antibodies immunization induces is critical for enhancing the vaccine.

Read Also: The University of Oxford Develops a Malaria Vaccine That Is 77% Effective

A possible explanation for reduced defense

Wardemann and her colleagues enrolled volunteers of European ancestry with no history of contact with malaria pathogens for this study. They infected the blood of these subjects with the vaccine strain’s killed Plasmodium sporozoites to better work out how T helper cells respond against CSP.

“To improve the vaccine, we need to understand which protective antibodies are induced by the immunization. But the production of such antibodies depends to a large extent on help from the so-called follicular T helper cells,” Wardemann explained. “They ensure that B cells transform into antibody-producing plasma cells and memory B cells.”

The research team closely looked at the induced follicular T helper cells that are specific to Plasmodium at the single-cell level. It especially honed in on the particular CSP sequences that are known to the T helper cell receptors.

Analyses carried out by the DKFZ researchers showed that the receptors of the T helper cells largely aimed at the CSP’s amino acids 311 to 333.

The more surprising finding was that there was almost a total absence of cross-reactivity between T-cell clones.

The T-cell receptors “highly specifically bind only the CSP epitopes of the vaccine strain used,” Wardemann stated. She noted that sequence polymorphisms in the native P. falciparum population occur mostly in this part 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,'” explained Wardemann.

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The immunologist noted that this finding probably explains why the defensive effect of the malaria vaccine quickly fades. A wider range of T helper cells should be tested in further vaccine development to see if their inducement would provide long-term protection against the malaria parasite, she added.

References

Clonal evolution and TCR specificity of the human TFH cell response to Plasmodium falciparum CSP

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