Development of novel malaria vaccine antigen targeting multiple stages of the plasmodium lifecycle. - development of a novel malaria vaccine antigen targeting multiple stages of the plasmodium…

The National Institute of Allergy and Infectious Diseases (NIAID) awarded Mercer University $230,463 on July 3, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to develop a novel malaria vaccine antigen targeting multiple stages of the Plasmodium lifecycle.

The research combines transmission-blocking and liver-stage vaccine approaches into a single fusion construct. The work evaluates transmission-blocking efficacy of the HSP90N' domain and MG1 peptide targeting female gametes, then fuses an optimal female-targeting antigen with the FG1 peptide targeting male gametes. This dual-target construct is linked with a recently developed triple-epitope liver-stage vaccine antigen to generate a multiple-stage vaccine antigen comprising five epitopes: female and male gamete antigens, an PFCSP NPNA repeat peptide, a P39 peptide targeting sporozoite-Kupffer cell traversal, and an HP1 peptide targeting sporozoite-hepatocyte invasion. The strategy aims to elicit broad protective immunity through a single antigen addressing multiple essential epitopes across the parasite lifecycle.

Mercer University, located in Macon, Georgia, is the recipient institution. Performance occurs in Macon, GA. The award period extends from July 3, 2026, through June 30, 2028.

Development of novel malaria vaccine antigen targeting multiple stages of the plasmodium lifecycle. - development of a novel malaria vaccine antigen targeting multiple stages of the plasmodium lifecycle. Project summary previously, using a phage peptide display library technique, our group identified mimotope peptides that mimic the conformation of plasmodium sporozoite ligands essential for liver infection. Notably, these small peptides elicit protective immunity by inducing antibodies that neutralize sporozoites. Using a similar approach, we identified two peptides, FG1 and MG1, which structurally mimic ligands employed by male and female gametes to facilitate parasite fertilization in the mosquito midgut. Antibodies generated against each peptide specifically bind to their corresponding gametes and markedly inhibit fertilization, thereby blocking mosquito transmission. Using the anti-MG1 antibody, we further identified the plasmodium heat-shock- protein 90 n'-terminal atpase domain (HSP90N') as the female gamete fertilization ligand and a potential transmission-blocking vaccine (TBV) antigen. We propose to 1) evaluate the transmission-blocking efficacy of the HSP90N' domain and the MG1 peptide to select an optimal female-targeting antigen, and then fuse IT with the male-targeting FG1 peptide to generate a dual-target TBV antigen; and 2) develop a multiple-stage vaccine antigen by linking the dual epitope TBV construct with our recently developed triple-epitope liver-stage vaccine antigen. The final fusion vaccine antigen will comprise: (i) a female gamete antigen (HSP90N' or MG1), (II) the FG1 peptide targeting male gametes, (III) the pfcsp npna repeat peptide, (IV) the P39 peptide targeting sporozoite-kupffer cell traversal, and (v) the HP1 peptide targeting sporozoite-hepatocyte invasion. We anticipate that this strategy will enhance malaria control by eliciting broad protective immunity through a single antigen targeting multiple essential epitopes across the plasmodium life cycle.