Functional Conservation of the AMA1 Host-Cell Invasion Ligand Between P. falciparum and P. vivax: A Novel Platform to Accelerate Vaccine and Drug Development

What is it about?

Plasmodium vivax and P. falciparum malaria species have diverged significantly in their interactions involved in infection and mechanisms of host-cell invasion. One protein common to both is the merozoite invasion ligand called AMA1. While the general structure of AMA1 is similar between species, their sequences are divergent. Surprisingly, we found that the function of AMA1 was conserved between species - PvAMA1 could replace PfAMA1 and retain function. Results indicate significant molecular flexibility in AMA1 enabling conserved function despite substantial sequence divergence across species. This provides powerful new tools to quantify the inhibitory activities of antibodies or drugs targeting PvAMA1, opening new opportunities for vaccine and therapeutic development against P. vivax.

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Why is it important?

malaria caused by P. vivax is a major global health problem, and in many parts of Asia and the Americas P. vivax is the predominant form of malaria. A greater understanding the molecular basis of P. vivax invasion, and how it diverges from P. falciparum, is needed to advance the development of vaccines. Our findings provide valuable new insights into the functional conservation and divergence of AMA1 in P. vivax and P. falciparum, and establish powerful new tools to dissect molecular interactions and to accelerate the development of vaccines and therapeutics based on PvAMA1. P. falciparum expressing PvAMA1 provide a powerful tool to evaluate functional inhibitory antibodies for vaccine development, refinement, and evaluation in a way that has not previously been possible.

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