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Developmental biology of sporozoite-host interactions in Plasmodium falciparum malaria: implications for vaccine design.

ABSTRACT: The Plasmodium falciparum sporozoite infects different types of cells in a mosquito's salivary glands and human epithelial and Kuppfer cells and hepatocytes. These become differentiated later on, transforming themselves into the invasive red blood cell form, the merozoite. The ability of sporozoites to interact with different types of cells requires a wide variety of mechanisms allowing them to survive in both hosts: mobility, receptor-ligand interactions with different cellular receptors, and transformation and development into other invasive parasite forms, which are vitally important for parasite survival. Sporozoite complexity is reflected in the large quantity of proteins that can be expressed. Some of them have been extensively studied, such as CSP, TRAP, STARP, LSA-1, LSA-3, SALSA, SPECT1, SPECT2, MAEBL, and SPATR, due to their importance in infection and their potential use as vaccines. Our work has been focused on the search for the molecular mechanisms of parasite-host cellular receptor-ligand interactions by identifying amino acid sequences and the critical binding residues from these proteins relevant to parasite invasion. Once such sequences have been identified, it will be possible to modify them to induce a strong immune response against P. falciparum in the experimental Aotus monkey model. This all leads towards developing multistage, multicomponent, subunit-based vaccines that will be effective in eradicating or controlling malaria caused by P. falciparum.

SUBMITTER: Garcia JE

PROVIDER: S-EPMC1592691 | biostudies-literature | 2006 Oct

REPOSITORIES: biostudies-literature

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Developmental biology of sporozoite-host interactions in Plasmodium falciparum malaria: implications for vaccine design.

Garcia Javier E JE Puentes Alvaro A Patarroyo Manuel E ME

Clinical microbiology reviews 20061001 4

The Plasmodium falciparum sporozoite infects different types of cells in a mosquito's salivary glands and human epithelial and Kuppfer cells and hepatocytes. These become differentiated later on, transforming themselves into the invasive red blood cell form, the merozoite. The ability of sporozoites to interact with different types of cells requires a wide variety of mechanisms allowing them to survive in both hosts: mobility, receptor-ligand interactions with different cellular receptors, and t ...[more]

PMID: 17041140

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Project description:MB2 protein is a sporozoite surface antigen on the human malaria parasite Plasmodium falciparum. MB2 was identified by screening a P. falciparum sporozoite cDNA expression library using immune sera from a protected donor immunized via the bites of P. falciparum-infected irradiated mosquitoes. It is not known whether natural exposure to P. falciparum also induces the anti-MB2 response and if this response differs from that in protected individuals immunized via the bites of P. falciparum infected irradiated mosquitoes. The anti-MB2 antibody response may be part of a robust protective response against the sporozoite.Fragments of polypeptide regions of MB2 were constructed as recombinant fusions sandwiched between glutathione S-transferase and a hexa histidine tag for bacterial expression. The hexa histidine tag affinity purified proteins were used to immunize rabbits and the polyclonal sera evaluated in an in vitro inhibition of sporozoite invasion assay. The proteins were also used in immunoblots with sera from a limited number of donors immunized via the bites of P. falciparum infected irradiated mosquitoes and plasma and serum obtained from naturally exposed individuals in Kenya.Rabbit polyclonal antibodies targeting the non-repeat region of the basic domain of MB2 inhibited sporozoites entry into HepG2-A16 cells in vitro. Analysis of serum from five human volunteers that were immunized via the bites of P. falciparum infected irradiated mosquitoes that developed immunity and were completely protected against subsequent challenge with non-irradiated parasite also had detectable levels of antibody against MB2 basic domain. In contrast, in three volunteers not protected, anti-MB2 antibodies were below the level of detection. Sera from protected volunteers preferentially recognized a non-repeat region of the basic domain of MB2, whereas plasma from naturally-infected individuals also had antibodies that recognize regions of MB2 that contain a repeat motif in immunoblots. Sequence analysis of eleven field isolates and four laboratory strains showed that these antigenic regions of the basic domain of the MB2 gene are highly conserved in parasites obtained from different parts of the world. Moreover, anti-MB2 antibodies also were detected in the plasma of 83% of the individuals living in a malaria endemic area of Kenya (n = 41).A preliminary analysis of the human humoral response against MB2 indicates that it may be an additional highly conserved target for immune intervention at the pre-erythrocytic stage of P. falciparum life cycle.

Dataset Information

Developmental biology of sporozoite-host interactions in Plasmodium falciparum malaria: implications for vaccine design.

Publications

Developmental biology of sporozoite-host interactions in Plasmodium falciparum malaria: implications for vaccine design.

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