Malaria is a devastating disease with a broad global impact. One of the demographics impacted the most is pregnant women, who are more susceptible to malaria, especially in their first pregnancy.(1) Malaria in pregnancy can cause many adverse health outcomes such as low birth weight, anaemia and increased mortality. Furthermore, no malaria vaccines have been certified for use during pregnancy, reducing protective options.
Malaria is primarily caused by the parasite P. falciparum, which infects red blood cells. These infected red blood cells exhibit a protein called PfEMP1. If antibodies can bind to PfEMP1, it allows the immune system to destroy the infected red blood cell. One major consideration for the efficacy of the antibody binding to PfEMP1 is the composition of an N-linked glycan present on the antibody.(2) Analysing PfEMP1-specific antibodies presents a challenge due to their low, unknown, concentration and structural diversity. Established methods often analyse the total antibody titre or employ multiple laborious experiments to determine glycan composition.
By combining a plate-based separation with a liquid chromatography-mass spectrometry approach, it is possible to determine the composition of the glycan present on the PfEMP1-specifc antibodies efficiently. Fragmentation methods can be used to verify the composition. Excitingly, the composition of the glycan, specifically the presence of fucose, can be linked to the degree of protection women have to malaria in pregnancy. Additionally, the results can be compared to established plate-based approaches and demonstrate increased sensitivity and precision. This enables a deeper understanding of the immune response to malaria in pregnancy and may pave the way to new preventative medicines.
References
1. Rogerson SJ et al. Malaria in pregnancy: pathogenesis and immunity. Lancet Infectious Diseases 2007 Feb 1; 7(2):105–17
2. Pereira NA et al. The “less-is-more” in therapeutic antibodies: Afucosylated anti-cancer antibodies with enhanced antibody-dependent cellular cytotoxicity. Mabs. 2018 Jul 4; 10(5):693.