fusions, where the antigen is displayed in a repetitive fashion on the surface and the fusion partner is somewhat buried \[[@bib53],[@bib54]\]. In the case of Pfs25:Grl1p and Pfs48/45^10C^:Grl1p, the similar or greater magnitude of the antibody response against the Grl1p component compared with the antigen component suggests that the proteins do not form such a structure. Co-crystal structures of transmission-blocking antibodies (generated against a plant-produced Pfs25 VLP in human immunoglobulin loci transgenic mice) with Pfs25 produced in human cells showed that the antibodies recognized two distinct immunogenic sites, one of which broadly overlapped with the 4B7 antibody epitope \[[@bib14]\]. These sites did not overlap with the binding site of the transmission-blocking antibody co-crystallized with Pvs25 \[[@bib15]\]. The epitopes recognized by our polyclonal antibodies are unknown, although they include at least some transmission-blocking epitopes as shown by the results of the membrane-feeding assay. Nevertheless, it is difficult to predict the nature or structure of the fusion protein based on the two we have investigated. Both proteins are similar in being GPI-anchored surface proteins. The size of the protein or number of cysteines does not appear to predict correct folding or antigenicity, as Pfs25 has 22 cysteines over 172 amino acids (11 disulfide bonds) \[[@bib13],[@bib14]\] while Pfs48/45^10C^ has 10 cysteines over 268 amino acids. The elucidation of a high-resolution structure of an antigen-carrying G-SOME particle may enable structure-guided vaccine design to i) increase antigen accessibility and uniformity on the particle surface with a potential concomitant increase in potency and/or ii) a decrease in the accessibility of the Grl fusion partner to mitigate off-target immune responses.

Antigen-fusion proteins are not a new concept in recombinant vaccine design. Pfs25 fused to *Salmonella* flagellin was soluble in *E. coli*, though antibodies generated against the protein were not assessed for t