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 1:125. 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.