Impact of antigen and carrier substitution on the molecular weight and immunogenicity of the Pfs230D1-CRM197 malaria transmission-blocking vaccine.

A protein-protein conjugate of Pfs230D1-CRM197 is currently being developed as a malaria transmission-blocking vaccine. To generate the conjugate, antigen and carrier are substituted with a defined number of sulfhydryl and maleimide groups respectively. These modified proteins are combined to spontaneously form cross-linked conjugates of high molecular weight. Immunogenicity of the conjugate is dependent on the molecular weight of the conjugate which in turn is dependent on the number of sulfhydryl and maleimide modifications on the antigen and carrier respectively. To evaluate the range of modifications that would generate the desired conjugates, we synthesized a series of conjugates with varying levels of sulfhydryl and maleimide modifications on the two proteins. Mouse immunogenicity study of these conjugates adjuvanted with Matrix-M shows that the size of the conjugate and its immunogenicity depend on these parameters. Nevertheless, a broad range of these parameters generate highly immunogenic Pfs230D1 conjugates.