MSP2 is a glycosylphosphatidylinositol (GPI)-anchored protein expressed on the surface of Plasmodium falciparum merozoites. Antibodies targeting MSP2 play a critical role in malaria immunity by inhibiting parasite invasion of red blood cells . Key features include:
Structural properties: Intrinsically disordered protein with conserved N- and C-terminal regions flanking a central polymorphic domain .
Antigenic diversity: Two major allelic families (IC1/3D7 and FC27) drive strain-specific immune responses .
Studies in malaria-endemic regions demonstrate correlations between anti-MSP2 antibodies and clinical protection:
| Antibody Class | Association with Protection | Allelic Specificity | Source |
|---|---|---|---|
| IgG | Reduced incidence of malaria | Cross-reactive | |
| IgG3 | Strong correlation with protection | IC1/FC27-specific |
High IgG3 titers to MSP2’s conserved C-terminal region correlate with reduced parasite density .
Allele-specific responses are less predictive of protection than cross-reactive antibodies .
Neutralization: Blocks merozoite invasion by steric hindrance or direct binding to functional domains .
Opsonization: Enhances phagocytosis by macrophages and neutrophils .
A cohort study of 146 children in a malaria-endemic area revealed:
| MSP2 Allelic Type | IgG Sero-Positivity (%) | IgG3 High Levels (%) |
|---|---|---|
| IC1-like (Type A) | 65 | 20 |
| FC27-like (Type B) | 65 | 25 |
No significant allele-specific protection was observed, suggesting conserved epitopes are critical for broad immunity .
mAb 4D11/9G8: Targets MSP2’s conserved C-terminus; shows strong reactivity in Western blot and immunofluorescence assays .
mAb 9H4/6C9: Binds overlapping epitopes but exhibits weak parasite recognition due to epitope inaccessibility .
Antigenic variability: Polymorphic regions evade antibody responses, necessitating focus on conserved domains .
Assay limitations: ELISA-based detection of MSP2 antibodies may not reflect functional activity due to conformational epitopes .
Combination vaccines: MSP2 paired with CSP (Circumsporozoite Protein) enhances sterile protection in murine models .
Adjuvant strategies: Cytokine-driven class switching (e.g., IL-21) improves IgG3 production for sustained immunity .