Exploring the immune responses triggered by vaccine formulations containing the recombinant Schistosoma mansoni 14kDa fatty acid-binding protein.

Abstract

Many different Schistosoma antigens have been evaluated as vaccine candidates, including the recombinant form of the Schistosoma mansoni 14-kDa fatty acid-binding protein (rSm14). However, recombinant proteins often lack intrinsic immunostimulatory activity, a limitation that can be addressed by using vaccine formulations that contain adjuvants. In this work, we describe the immune response triggered by rSm14, a vaccine candidate against schistosomiasis currently under clinical trial, formulated with either (i) Monophosphoryl Lipid A (MPLA), (ii) MPLA/Alum, or (iii) Freund's adjuvant. rSm14/MPLA and rSm14/MPLA/Alum formulations induced increased frequency of effector and memory CD4+ T and central memory CD8+ T cells, respectively. Both formulations induced significant production of rSm14-specific IgG and IgG1 antibodies, which could recognize the protein's native form. The rSm14/Freund's formulation elicited a robust immune response characterized by increased levels of IFN-γ, TNF, IgG, IgG1, and IgG2c antibodies, and expansion of memory B cell. These soluble factors have been implicated in the efficacy of Sm14-based vaccines. Despite inducing both humoral and cellular immune responses, the different formulations did not impact worm burden and the number of eggs trapped in the liver and intestine. Altogether, our findings indicate a limitation in the use of the molecules assessed in this study, such as IFN-γ, TNF, and specific antibodies, as correlates of protection and vaccine efficacy.