Lipid interactions modulate the structural and antigenic properties of the C-terminal domain of the malaria antigen merozoite surface protein 2

5 years ago

Lipid interactions modulate the structural and antigenic properties of the C-terminal domain of the malaria antigen merozoite surface protein 2

Sreedam C. Das, Raymond S. Norton, Robin F. Anders, Jeffrey Seow, Rodrigo A.V. Morales, Ravindu Dissanayake, Bankala Krishnarjuna, Christopher A. MacRaild

Merozoite surface protein 2 (MSP2) is a highly abundant, GPI-anchored antigen on the malaria parasite Plasmodium falciparum. MSP2 induces an immune response in the context of natural infections and vaccine trials, and these responses are associated with protection from parasite infection. Recombinant MSP2 is highly disordered in solution but antigenic analyses suggest that it is more ordered on the merozoite surface. We have shown previously that the interaction of recombinant full-length MSP2 with lipid surfaces induces a conformational change in the conserved N-terminal region of MSP2, which contributes to epitope masking in this region. To explore the impacts of lipid interactions on the conformation and antigenicity of the conserved C-terminal region of MSP2, a construct corresponding to this domain, MSP2172–221, was designed. NMR studies indicate that many residues in MSP2172–221 interact with DPC micelles, including some in epitopes recognised by C-terminal-specific monoclonal antibodies, but, in contrast to the MSP2 N-terminus, there is no indication of stable helical conformation. The binding affinities of a panel of monoclonal antibodies indicate that MSP2172–221 is antigenically similar to full-length MSP2 and show that liposome conjugation alters the antigenicity in a manner that may mimic native MSP2 on the merozoite surface. These findings highlight the impact of lipid interactions on the conformation and antigenicity of MSP2172–221 and will assist in the design of recombinant MSP2 immunogens for use as malaria vaccine candidates. Databases Resonance assignments are available in the BioMagResBank (BMRB) database under the accession number 27134. MSP2 from the malaria parasite Plasmodium falciparum induces a protective immune response. Tethering the conserved C-terminal region (MSP2172–221) to liposomes induced an antigenic state that was more similar to the parasite antigen. Lipid-conjugated MSP2 may represent a useful vaccine formulation.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/febs.14135