Somatic hypermutation-mediated paratope flexibility improves the cross-reactivity of human malaria antibodies.

A preprint abstract from biorxiv.org discusses the role of somatic hypermutation (SHM) in the development of antibodies that target the circumsporozoite protein on sporozoites of the malaria parasite Plasmodium falciparum (PfCSP). The study found that SHM reduces the flexibility of the unbound antibodies but increases the flexibility of the antigen-bound complex, making it easier for the antibodies to bind to the antigen. However, the study also identified an inverse relation between antibody affinity and serum stability, which limits the protective capacity of these antibodies. The research provides molecular level evidence for the different roles that the SHM process plays in increasing antibody affinity and cross-reactivity, and demonstrates how antibody affinity maturation can negatively impact antibody stability and function. [Extracted from the article]