4JLR

Crystal structure of a designed Respiratory Syncytial Virus Immunogen in complex with Motavizumab

Summary for 4JLR

• Entry DOI: 10.2210/pdb4jlr/pdb
• Descriptor: Motavizumab Fab heavy chain, Motavizumab Fab light chain, RSV_1Isea designed scaffold, ... (5 entities in total)
• Functional Keywords: antibody, designed immunogen, specific binding, rsv f protein, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 123777.45

Authors

Rupert, P.B.,Correia, B.,Schief, W.,Strong, R.K. (deposition date: 2013-03-12, release date: 2014-02-05, Last modification date: 2024-10-30)

Primary citation

Correia, B.E.,Bates, J.T.,Loomis, R.J.,Baneyx, G.,Carrico, C.,Jardine, J.G.,Rupert, P.,Correnti, C.,Kalyuzhniy, O.,Vittal, V.,Connell, M.J.,Stevens, E.,Schroeter, A.,Chen, M.,Macpherson, S.,Serra, A.M.,Adachi, Y.,Holmes, M.A.,Li, Y.,Klevit, R.E.,Graham, B.S.,Wyatt, R.T.,Baker, D.,Strong, R.K.,Crowe, J.E.,Johnson, P.R.,Schief, W.R.
Proof of principle for epitope-focused vaccine design.
Nature, 507:201-206, 2014

PubMed Abstract: Vaccines prevent infectious disease largely by inducing protective neutralizing antibodies against vulnerable epitopes. Several major pathogens have resisted traditional vaccine development, although vulnerable epitopes targeted by neutralizing antibodies have been identified for several such cases. Hence, new vaccine design methods to induce epitope-specific neutralizing antibodies are needed. Here we show, with a neutralization epitope from respiratory syncytial virus, that computational protein design can generate small, thermally and conformationally stable protein scaffolds that accurately mimic the viral epitope structure and induce potent neutralizing antibodies. These scaffolds represent promising leads for the research and development of a human respiratory syncytial virus vaccine needed to protect infants, young children and the elderly. More generally, the results provide proof of principle for epitope-focused and scaffold-based vaccine design, and encourage the evaluation and further development of these strategies for a variety of other vaccine targets, including antigenically highly variable pathogens such as human immunodeficiency virus and influenza.

PubMed: 24499818
DOI: 10.1038/nature12966

Experimental method

X-RAY DIFFRACTION (2.71 Å)