Projects per year
Abstract
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 allows all MSP2 alleles to be categorized into the 3D7 or FC27 family. Previously it has been shown that epitope accessibility differs between lipid-bound and lipid-free MSP2, suggesting that lipid interactions modulate the conformation and antigenicity in a way that may better mimic native MSP2 on the merozoite surface. Therefore, we have immunised mice with MSP2 engrafted onto liposomes using a C-terminal tether that mimics the native GPI anchor. To improve the immunogenicity of the formulated antigen, liposomes were supplemented with Pathogen Associated Molecular Pattern molecules, specifically agonists of the Toll-like receptor 4 (TLR4) or TLR2. Induced antibodies were directed mostly towards conserved epitopes, predominantly in the conserved C-terminal region of MSP2. We also found that immunisation with a combination of 3D7 and FC27 MSP2 enhanced antibody responses to conserved epitopes, and that the overall responses of mice immunised with MSP2-engrafted liposomes were comparable in magnitude to those of mice immunised with MSP2 formulated in Montanide ISA720. The antibodies elicited in mice by immunising with MSP2-engrafted liposomes recognised the native form of parasite MSP2 on western blots and were found to be cross-reactive with isolated 3D7 and FC27 merozoites when investigated by ELISA. The liposome-tethered MSP2 induced higher titres of complement-fixing antibodies to 3D7 and FC27 MSP2 than did MSP2 formulated in Montanide ISA720. Our results indicate that liposomal formulation represents a viable strategy for eliciting a strong immune response that favours conserved epitopes in MSP2 and thus a strain-transcendent immune response.
Original language | English |
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Pages (from-to) | 1746-1757 |
Number of pages | 12 |
Journal | Vaccine |
Volume | 39 |
Issue number | 12 |
DOIs | |
Publication status | Published - 19 Mar 2021 |
Keywords
- Complement fixation
- Conserved epitope
- Immune response
- Liposome
- Malaria
- Merozoite surface protein 2
Projects
- 1 Finished
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Generating an effective vaccine response against the intrinsically unstructured malaria antigen Merozoite Surface Protein 2
Norton, R. (Primary Chief Investigator (PCI)), MacRaild, C. (Chief Investigator (CI)) & Richards, J. (Chief Investigator (CI))
NHMRC - National Health and Medical Research Council (Australia)
1/01/13 → 31/12/15
Project: Research