Can antibody conjugated nanomicelles alter the prospect of antibody targeted therapy against schistosomiasis mansoni?

Background: CLA (conjugated linoleic acid)-mediated activation of the schistosome tegument-associated sphingomyelinase and consequent disruption of the outer membrane might allow host antibodies to access the apical membrane antigens. Here, we investigated a novel approach to enhance specific antibody delivery to concealed surface membrane antigens of Schistosoma mansoni utilising antibody-conjugated-CLA nanomicelle technology. Methodology/Principal findings: We invented and characterised an amphiphilic CLA-loaded whey protein co-polymer (CLA-W) as an IV injectable protein nanocarrier. Rabbit anti-Schistosoma mansoni infection (anti-SmI) and anti-Schistosoma mansoni alkaline phosphatase specific IgG antibodies were purified from rabbit sera and conjugated to the surface of CLA-W co-polymer to form antibody-conjugated-CLA-W nanomicelles (Ab-CLA-W). We investigated the schistosomicidal effects of CLA-W and Ab-CLA-W in a mouse model of Schistosoma mansoni against early and late stages of infection. Results showed that conjugation of nanomicelles with antibodies, namely anti-SmI, significantly enhanced the micelles' schistosomicidal and anti-pathology activities at both the schistosomula and adult worm stages of the infection resulting in 64.6%-89.9% reductions in worm number; 72.5–94% and 66.4–85.2% reductions in hepatic eggs and granulomas, respectively. Treatment induced overall improvement in liver histopathology, reducing granuloma size and fibrosis and significantly affecting egg viability. Indirect immunofluorescence confirmed CLA-W-mediated antigen exposure on the worm surface. Electron microscopy revealed extensive ultrastructural damage in worm tegument induced by anti-SmI-CLA-W. Conclusion/Significance: The novel antibody-targeted nano-sized CLA delivery system offers great promise for treatment of Schistosoma mansoni infection and control of its transmission. Our in vivo observations confirm an immune-mediated enhanced effect of the schistosomicidal action of CLA and hints at the prospect of nanotechnology-based immunotherapy, not only for schistosomiasis, but also for other parasitic infections in which chemotherapy has been shown to be immune-dependent. The results propose that the immunodominant reactivity of the anti-SmI serum, Schistosoma mansoni fructose biphosphate aldolase, SmFBPA, merits serious attention as a therapeutic and vaccine candidate. Author summary: Schistosomiasis (Bilharzia) is an acute and chronic parasitic disease caused by blood flukes of the genus Schistosoma. Conjugated linoleic acid (CLA) is considered a natural fatty acid activator of sphingomyelinase enzyme that helps to expose the normally hidden parasite surface antigens to antibody binding and subsequent worm killing. Two rabbit anti-schistosome antibodies: anti-Schistsosoma mansoni infection (anti-SmI) and anti- Schistsosoma mansoni alkaline phosphatase antibodies were coupled to the surface of CLA-whey protein co-polymer (CLA-W) to target the CLA-W to the parasite membrane. We assessed the in vivo effects of CLA-W in their non-coupled and antibody-coupled forms against the early and late stages of infection. The injection of anti-SmI-coupled CLA-W produced the highest effects against both early stage schistosome larvae and late stage adult worms, resulting in significant reductions in worms and eggs burdens. By electron microscope, the adult worm tegument showed severe injury and evidence of cell death. Antigens were exposed on the worm surface to antibody binding as indicated by the increase in the worm surface immunofluorescence staining. The study highlights the promising potential of the antibody-coupled CLA-W co-polymer for treatment of schistosomiasis and control of its transmission. [ABSTRACT FROM AUTHOR]