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Most studies on human immunity to malaria have focused on the roles of immunoglobulin G (IgG), whereas the roles of IgM remain undefined. Analyzing multiple human cohorts to assess the dynamics of malaria-specific IgM during experimentally induced and naturally acquired malaria, we identified IgM activity against blood-stage parasites. We found that merozoite-specific IgM appears rapidly in Plasmodium falciparum infection and is prominent during malaria in children and adults with lifetime exposure, together with IgG. Unexpectedly, IgM persisted for extended periods of time; we found no difference in decay of merozoite-specific IgM over time compared to that of IgG. IgM blocked merozoite invasion of red blood cells in a complement-dependent manner. IgM was also associated with significantly reduced risk of clinical malaria in a longitudinal cohort of children. These findings suggest that merozoite-specific IgM is an important functional and long-lived antibody response targeting blood-stage malaria parasites that contributes to malaria immunity.

Original publication

DOI

10.1126/sciadv.aax4489

Type

Journal article

Journal

Science advances

Publication Date

25/09/2019

Volume

5

Addresses

Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia.

Keywords

Humans, Plasmodium falciparum, Malaria, Falciparum, Immunoglobulin G, Immunoglobulin M, Antibodies, Protozoan, Antigens, Protozoan, Immunity, Antibody Formation, Antibody Specificity, Adolescent, Adult, Middle Aged, Female, Male, Host-Parasite Interactions, Young Adult