Malaria memory
NIMR scientists have shown that long-lived immune responses can be induced by malaria infection. The research is published in PLoS Pathogens.
Malaria causes considerable human suffering due to the associated high mortality, morbidity and reduced economic productivity in malaria-affected areas. Anti-malarial drugs and insecticide-treated nets are currently used to control malaria, but these can be expensive and can be rendered ineffective by the development of resistance. The development of vaccines is therefore important in the drive to eradicate malaria. Antibodies play a critical role in naturally acquired immunity to the blood stages of malaria, and therefore induction of a long-lasting protective antibody response against these stages is the major focus of vaccine development. However, there are indications that some antigens of the malaria parasite, Plasmodium, may not induce long-lived antibody responses. This could hamper vaccine efficacy.
Jean Langhorne's group in NIMR's Division of Parasitology, has investigated whether malaria infection does affect the development of specific antibody responses by studying the kinetics, duration and characteristics of the two cell types responsible for their production. Because the cellular mechanisms underlying B cell and antibody responses are difficult to study in human infections, they used a mouse model of malaria, Plasmodium chabaudi. Despite the fact that antibody levels drop significantly after an acute blood-stage infection, memory B cells and plasma cells specific for a protein expressed on the surface of the merozoite stage, the C-terminal region of Merozoite Surface Protein 1 (MSP1), are retained more than eight months later, and both long-lived antibody-secreting cells and functional malaria-specific memory B cells specific for MSP1 can be made after a single infection.
Furthermore, a classical memory response was elicited upon re-challenge with the homologous parasite, confirming that the memory B cells generated are functional. Using cyclophosphamide treatment to discriminate between long-lived and short-lived plasma cells, long-lived cells secreting MSP1-specific IgG were found in both bone marrow and in spleens of infected mice; organs inaccessible for study in infected humans. Importantly for vaccine development, the presence of long-lived cells was independent of chronic infection, as removal of parasites with anti-malarial drugs had no impact on their numbers. Thus, in this model of malaria, functional Plasmodium-specific memory B cells and long-lived antibody secreting cells can both be generated, in addition to short-lived antibody-secreting cells induced in acute infection.
"Our studies are very encouraging for vaccine development for human malaria infections. Vaccines have to induce antibody responses that are maintained for long periods of time. Our data indicate that despite the short-lived nature of some antibody responses early after an infection, long-lived antibody-secreting cells and functional memory B cells, which are the key components of protective immunological memory, can be induced in this malaria infection."
Jean Langhorne
Original article
The research findings are published in full in:
Francis Maina Ndungu, Emma Tamsin Cadman, Joshua Coulcher, Eunice
Nduati, Elisabeth Couper, Douglas William MacDonald, Dorothy Ng and Jean
Langhorne (2009)
Functional memory B cells and long-lived plasma cells are
generated after a single Plasmodium chabaudi infection in mice
PLoS Pathogens,
5(12): e1000690. Fulltext of article
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[17 December 2009]