Peptide mimics as surrogate immunogens of mosquito midgut carbohydrate malaria transmission blocking targets

Transmission blocking vaccines (TBV) against mosquito midgut carbohydrate epitopes is a promising approach to curbing the spread of malaria. However, carbohydrates as immunogens can be problematic. Via the malaria transmission blocking monoclonal antibody, MG96, we isolated dodecapeptide mimics of the conserved, nominal mosquito carbohydrate epitope from a peptide-display library. Two peptide clones, bearing a constrained, consensus motif competitively inhibited MG96 reactivity with its nominal midgut microvillar antigen. However, rabbit polyclonal antisera against these synthetic peptides recognized heterologous mosquito midgut carbohydrate and protein epitopes along the midgut basal lamina. Consequently, antisera did not block parasite development within the mosquito vector. Therefore, it is imperative that peptides not only need to be functional mimics but also complete mimotopes to effectively direct the vertebrate immune response towards the nominal, protective carbohydrate epitope on mosquito microvilli.