7PI3

PfCyRPA bound to Fab fragments from monoclonal antibodies Cy.003, Cy.004 and Cy.007

Summary for 7PI3

• Entry DOI: 10.2210/pdb7pi3/pdb
• Descriptor: Cysteine-rich protective antigen, Monoclonal antibody Cy.003 heavy chain, Monoclonal antibody Cy.003 light chain, ... (8 entities in total)
• Functional Keywords: malaria, plasmodium falciparum, monoclonal antibody, vaccine, immune system
• Biological source: Plasmodium falciparum 3D7; More
• Total number of polymer chains: 28
• Total formula weight: 758093.88

Authors

Ragotte, R.J.,Higgins, M.K. (deposition date: 2021-08-19, release date: 2022-02-09, Last modification date: 2024-01-31)

Primary citation

Ragotte, R.J.,Pulido, D.,Lias, A.M.,Quinkert, D.,Alanine, D.G.W.,Jamwal, A.,Davies, H.,Nacer, A.,Lowe, E.D.,Grime, G.W.,Illingworth, J.J.,Donat, R.F.,Garman, E.F.,Bowyer, P.W.,Higgins, M.K.,Draper, S.J.
Heterotypic interactions drive antibody synergy against a malaria vaccine candidate.
Nat Commun, 13:933-933, 2022

PubMed Abstract: Understanding mechanisms of antibody synergy is important for vaccine design and antibody cocktail development. Examples of synergy between antibodies are well-documented, but the mechanisms underlying these relationships often remain poorly understood. The leading blood-stage malaria vaccine candidate, CyRPA, is essential for invasion of Plasmodium falciparum into human erythrocytes. Here we present a panel of anti-CyRPA monoclonal antibodies that strongly inhibit parasite growth in in vitro assays. Structural studies show that growth-inhibitory antibodies bind epitopes on a single face of CyRPA. We also show that pairs of non-competing inhibitory antibodies have strongly synergistic growth-inhibitory activity. These antibodies bind to neighbouring epitopes on CyRPA and form lateral, heterotypic interactions which slow antibody dissociation. We predict that such heterotypic interactions will be a feature of many immune responses. Immunogens which elicit such synergistic antibody mixtures could increase the potency of vaccine-elicited responses to provide robust and long-lived immunity against challenging disease targets.

PubMed: 35177602
DOI: 10.1038/s41467-022-28601-4

Experimental method

X-RAY DIFFRACTION (3.269 Å)