9CR9

Crystal structure of MA6 Fab in complex with PfCSP repeat region peptide NPNA3

Summary for 9CR9

• Entry DOI: 10.2210/pdb9cr9/pdb
• Descriptor: MA6 Fab heavy chain, MA6 Fab light chain, Circumsporozoite protein (NPNA)3 repeat region peptide, ... (4 entities in total)
• Functional Keywords: circumsporozoite protein, pfcsp, csp, protective, neutralizing, antibody, fab, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 6
• Total formula weight: 99468.49

Authors

Rush, S.A.,McLellan, J.S. (deposition date: 2024-07-21, release date: 2025-07-09, Last modification date: 2025-08-13)

Primary citation

McDaniel, J.R.,Voss, W.N.,Bowyer, G.,Rush, S.A.,Spencer, A.J.,Bellamy, D.,Ulaszewska, M.,Goike, J.,Gregory, S.,King, C.R.,McLellan, J.S.,Hill, A.V.S.,Georgiou, G.,Ewer, K.J.,Ippolito, G.C.
Repertoire, function, and structure of serological antibodies induced by the R21/Matrix-M malaria vaccine.
J.Exp.Med., 222:-, 2025

PubMed Abstract: The World Health Organization (WHO) recently recommended the programmatic use of the R21/Matrix-M vaccine for Plasmodium falciparum malaria prevention in children living in malaria-endemic areas. To determine its effects on humoral immunity, we conducted a proteomic analysis of polyclonal IgG antibodies directed against the NANP tetrapeptide of the circumsporozoite protein (CSP), which comprises the vaccine's core immunogen. In 10 malaria-naïve adult volunteers, R21/Matrix-M induced polarized IgG anti-NANP repertoires, heavily skewed for IGHV3-30/3-33 genes bearing minimal somatic mutation, which remained static in composition following a controlled human malaria infection challenge. Notably, these vaccine-generated antibodies cross-reacted with another protective CSP epitope, the N-terminal junction region, despite its absence from the R21 construct. NANP-specific IGHV3-30/3-33 mAbs mined from polyclonal IgG repertoires blocked sporozoite invasion in vitro and prevented parasitemia in vivo. Overall, R21/Matrix-M elicits polarized, minimally mutated, polyclonal IgG responses that can target multiple protective CSP epitopes, offering molecular insight into the serological basis for its demonstrated efficacy against P. falciparum malaria.

PubMed: 40719751
DOI: 10.1084/jem.20241908

Experimental method

X-RAY DIFFRACTION (1.8 Å)