7TXW

Crystal structure of the complex of the malaria sexual stage protein and vaccine target Pfs25 with the Fab fragment of a transmission blocking antibody 1G2

Summary for 7TXW

• Entry DOI: 10.2210/pdb7txw/pdb
• Descriptor: Fab fragment of monoclonal antibody 1G2 light chain, Fab fragment of monoclonal antibody 1G2 heavy chain, Ookinete surface protein P25, ... (8 entities in total)
• Functional Keywords: malaria, transmission blocking vaccine, immune system
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 3
• Total formula weight: 67596.14

Authors

Singh, K.,Gittis, A.G.,Garboczi, D.N. (deposition date: 2022-02-10, release date: 2023-04-12, Last modification date: 2024-04-03)

Primary citation

MacDonald, N.J.,Singh, K.,Reiter, K.,Nguyen, V.,Shimp Jr., R.,Gittis, A.G.,Chen, B.,Burkhardt, M.,Zhang, B.,Wang, Z.,Herrera, R.,Moler, M.,Lee, D.Y.,Orr-Gonzalez, S.,Herrod, J.,Lambert, L.E.,Rausch, K.M.,Muratova, O.,Jones, D.S.,Wu, Y.,Jin, A.J.,Garboczi, D.N.,Duffy, P.E.,Narum, D.L.
Structural and immunological differences in Plasmodium falciparum sexual stage transmission-blocking vaccines comprised of Pfs25-EPA nanoparticles.
Npj Vaccines, 8:56-56, 2023

PubMed Abstract: Development of a malaria vaccine that blocks transmission of different parasite stages to humans and mosquitoes is considered critical for elimination efforts. A vaccine using Pfs25, a protein on the surface of zygotes and ookinetes, is under investigation as a transmission-blocking vaccine (TBV) that would interrupt parasite passage from mosquitoes to humans. The most extensively studied Pfs25 TBVs use Pichia pastoris-produced recombinant forms of Pfs25, chemically conjugated to a recombinant carrier protein, ExoProtein A (EPA). The recombinant form of Pfs25 first used in humans was identified as Pfs25H, which contained a total of 14 heterologous amino acid residues located at the amino- and carboxyl-termini including a His6 affinity tag. A second recombinant Pfs25, identified as Pfs25M, was produced to remove the heterologous amino acid residues and conjugated to EPA (Pfs25M-EPA). Here, monomeric Pfs25M was characterized biochemically and biophysically for identity, purity, and integrity including protein structure to assess its comparability with Pfs25H. Although the biological activities of Pfs25H and Pfs25M, whether generated by monomeric forms or conjugated nanoparticles, appeared similar, fine-mapping studies with two transmission-blocking monoclonal antibodies detected structural and immunological differences. In addition, evaluation of antisera generated against conjugated Pfs25H or Pfs25M nanoparticles in nonhuman primates identified polyclonal IgG that recognized these structural differences.

PubMed: 37061547
DOI: 10.1038/s41541-023-00655-5

Experimental method

X-RAY DIFFRACTION (2.17 Å)