Malarial Antibody Detection with an Engineered Yeast Agglutination Assay

Malaria, a disease caused by the Plasmodium parasite carried by Anopheles mosquitoes, is commonly diagnosed by microscopy of peripheral blood smears and with rapid diagnostic tests. Both methods show limited detection of low parasitemia that may maintain transmission and hinder malaria elimination. We have developed a novel agglutination assay in which modified Saccharomyces cerevisiae cells act as antigen-displaying bead-like particles to capture malaria antibodies. The Epidermal Growth Factor-1 like domain (EGF1) of the Plasmodium falciparum merozoite surface protein-1 (PfMSP-119) was displayed on the yeast surface and shown to be capable of binding antimalaria antibodies. Mixed with a second yeast strain displaying the Z domain of Protein A from Staphylococcus aureus and allowed to settle in a round-bottomed well, the yeast produce a visually distinctive agglutination test result: a tight button at a low level of malarial antibodies, and a diffuse sheet when higher antibody levels are present. Positive agglutination results were observed in malaria-positive human serum to a serum dilution of 1:100 to 1:12500. Since the yeast cells are inexpensive to produce, the test may be amenable to local production in regions seeking malaria surveillance information to guide their elimination programs.

Automated summary

A novel agglutination assay using modified Saccharomyces cerevisiae cells as antigen-displaying particles was developed to capture malaria antibodies. The assay showed high sensitivity in detecting low parasitemia and can be produced at a low cost, making it suitable for local production in regions aiming to eliminate malaria.