Protective immune potential of multiple antigenic peptide (MAP) constructs comprising peptides that are shared by several cysteine peptidases against Schistosoma mansoni infection in mice

[Display omitted] •MAPs comprising peptide sequences shared by cysteine peptidases were tested in vaccine trials against Schistosoma mansoni challenge infection.•Both MAPs tested (MAP-1 and MAP-2) elicited a significant reduction in S. mansoni challenge worm burden.•While MAP-2 immunization yielded fewer (but more mature) eggs, MAP-1 immunization yielded higher egg numbers.•MAP-1 and MAP-2 elicited modest type 2-biased immune responses.•Immunization with papain elicited a reduction in parasite egg load, viability and granuloma number in liver and intestine.•MAP-1 and MAP-2 induced opposite effects on worm fecundity and egg traffic. In vaccine trials, Schistosoma mansoni cathepsin B1 (SmCB1), helminth cathepsins of the L family (e.g., SmCL3), and papain consistently induce highly significant reductions in challenge worm burden and egg viability, but generated no additive protective effects when used in combination. The protective capacity of the cysteine peptidases is associated with modest (SmCB1) and poor (cathepsins L) production of cytokines and antibodies, essentially of the type 2 axis, and is only marginally reduced upon use of proteolytically inactive enzymes. In this work, peptides shared by SmCB1, cathepsins of the L family, papain and other allergens were selected, synthesized as tetrabranched multiple antigen peptide constructs (MAP-1 and MAP-2), and used in two independent experiments to immunize outbred mice, in parallel with papain. The two peptides elicited significant (P < 0.05) reduction in challenge worm burden when compared to unimmunized mice, albeit lower than that achieved by papain. Protection was associated with modest serum type 2 cytokines and antibody levels in MAP-, and papain-immunized mice. Immunization with papain also elicited a reduction in parasite egg load, viability, and granuloma numbers in liver and intestine. MAP-1 and MAP-2 immunogens displayed some opposite effects- MAP-1 leading to higher egg numbers with poor vitality, whereas MAP-2 immunization yielded fewer eggs. Cysteine peptidase thus appear to carry peptides that elicit opposing outcomes, highlighting the difficulty of reaching fully fledged protection, unless a vaccine is based on carefully selected peptides and combined with an effective adjuvant.