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

doi:10.1093/infdis/jix583

. 2018 Jan 17;217(3):498-507.

doi: 10.1093/infdis/jix583.

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

Damien R Drew¹, Paul R Sanders¹, Gretchen Weiss¹, Paul R Gilson¹, Brendan S Crabb^{1

2

3}, James G Beeson^{1

2

3

4}

Affiliations

¹ Burnet Institute, Melbourne, Australia.
² Department of Medicine, University of Melbourne, Victoria, Australia.
³ Department of Microbiology and Immunology, University of Melbourne, Victoria, Australia.
⁴ Central Clinical School and Department of Microbiology, Monash University, Victoria, Australia.

PMID: 29165651
DOI: 10.1093/infdis/jix583

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

Damien R Drew et al. J Infect Dis. 2018.

. 2018 Jan 17;217(3):498-507.

doi: 10.1093/infdis/jix583.

Authors

Damien R Drew¹, Paul R Sanders¹, Gretchen Weiss¹, Paul R Gilson¹, Brendan S Crabb^{1

2

3}, James G Beeson^{1

2

3

4}

Affiliations

¹ Burnet Institute, Melbourne, Australia.
² Department of Medicine, University of Melbourne, Victoria, Australia.
³ Department of Microbiology and Immunology, University of Melbourne, Victoria, Australia.
⁴ Central Clinical School and Department of Microbiology, Monash University, Victoria, Australia.

PMID: 29165651
DOI: 10.1093/infdis/jix583

Abstract

Plasmodium vivax and P. falciparum malaria species have diverged significantly in receptor-ligand interactions and host-cell invasion. One protein common to both is the merozoite invasion ligand AMA1. While the general structure of AMA1 is similar between species, their sequences are divergent. Surprisingly, it was possible to genetically replace PfAMA1 with PvAMA1 in P. falciparum parasites. PvAMA1 complemented PfAMA1 function and supported invasion of erythrocytes by P. falciparum. Genetically modified P. falciparum expressing PvAMA1 evaded the invasion inhibitory effects of antibodies to PfAMA1, demonstrating species specificity of functional antibodies. We generated antibodies to recombinant PvAMA1 that effectively inhibited invasion, confirming the function of PvAMA1 in genetically modified parasites. 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.

Keywords: AMA1; Plasmodium; malaria; merozoite; vaccine.

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

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

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