Poster Presentation First Malaria World Congress 2018

Liposome conjugation potentiates the immune response towards conserved epitopes of the malaria vaccine candidate MSP2 (#422)

Sreedam C. Das 1 , Jason Price 2 , Ricardo Ataide 3 , Jeffrey Seow 1 , Vashti Irani 3 , Ines Atmosukarto 2 , Robin F. Anders 4 , Jack S. Richards 3 , Chris A. MacRaild 1 , Raymond S. Norton 1
  1. Department of Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia
  2. Lipotek Pty Ltd, Canberra, ACT 2601, Australia
  3. Centre for Biomedical Research, Burnet Institute, Melbourne, VIC 3004, Australia
  4. Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne , VIC 3086, Australia

Merozoite surface protein 2 (MSP2) is a highly abundant, GPI-anchored surface antigen on merozoites of the malaria parasite Plasmodium falciparum. It consists of highly conserved N- and C-terminal domains, and a central polymorphic region that categorizes all MSP2 alleles into two families, 3D7 and FC27.1,2 Clinical trials have demonstrated that recombinant MSP2 is immunogenic and induces protective responses against parasite infection.3,4 Nonetheless, the conformation of MSP2 on the merozoite surface is yet to be explored. The interaction of recombinant MSP2 with a range of lipid surfaces has been studied by NMR, showing that conserved regions interact with lipid although the central variable region is minimally affected.5,6 Epitope accessibility differs between lipid-bound and lipid-free MSP2, indicating that lipid interactions alter the conformation and antigenicity in a way that may better mimic native MSP2 on the merozoite surface.7,8 Therefore, we have immunised mice with MSP2 conjugated with different liposome formulations. It appears that induced antibodies are directed mostly towards conserved epitopes, which are mainly associated with conserved C-terminus MSP2; the induction of antibodies specific for the conserved region would be very effective strategy to overcome antigenic diversity. We also found that the combination of two allelic MSP2 induces stronger antibody responses than single allelic form, and the overall responses of liposome-conjugated groups are comparable in magnitude to those of Montanide-adjuvanted groups. The induced antibodies can recognize native MSP2 in a western blot, and assessment of the reactivity by ELISA and IFA, as well as functional assays are underway. Our results indicate that liposome conjugation represents a viable strategy for eliciting a strong immune response that favours conserved epitopes in MSP2 and does not require adjuvants.

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