7LUD

Crystal structure of Fab ADI-14442

Summary for 7LUD

• Entry DOI: 10.2210/pdb7lud/pdb
• Descriptor: ADI-14442 Fab Heavy chain, ADI-14442 Fab Light chain, SULFATE ION (3 entities in total)
• Functional Keywords: rsv f, fab, antibody, viral fusion protein, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 96197.13

Authors

Rush, S.A.,McLellan, J.S. (deposition date: 2021-02-22, release date: 2021-06-16, Last modification date: 2024-10-09)

Primary citation

Mukhamedova, M.,Wrapp, D.,Shen, C.H.,Gilman, M.S.A.,Ruckwardt, T.J.,Schramm, C.A.,Ault, L.,Chang, L.,Derrien-Colemyn, A.,Lucas, S.A.M.,Ransier, A.,Darko, S.,Phung, E.,Wang, L.,Zhang, Y.,Rush, S.A.,Madan, B.,Stewart-Jones, G.B.E.,Costner, P.J.,Holman, L.A.,Hickman, S.P.,Berkowitz, N.M.,Doria-Rose, N.A.,Morabito, K.M.,DeKosky, B.J.,Gaudinski, M.R.,Chen, G.L.,Crank, M.C.,Misasi, J.,Sullivan, N.J.,Douek, D.C.,Kwong, P.D.,Graham, B.S.,McLellan, J.S.,Mascola, J.R.
Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein induces genetically and antigenically diverse antibody responses.
Immunity, 54:769-780.e6, 2021

PubMed Abstract: An effective vaccine for respiratory syncytial virus (RSV) is an unrealized public health goal. A single dose of the prefusion-stabilized fusion (F) glycoprotein subunit vaccine (DS-Cav1) substantially increases serum-neutralizing activity in healthy adults. We sought to determine whether DS-Cav1 vaccination induces a repertoire mirroring the pre-existing diversity from natural infection or whether antibody lineages targeting specific epitopes predominate. We evaluated RSV F-specific B cell responses before and after vaccination in six participants using complementary B cell sequencing methodologies and identified 555 clonal lineages. DS-Cav1-induced lineages recognized the prefusion conformation of F (pre-F) and were genetically diverse. Expressed antibodies recognized all six antigenic sites on the pre-F trimer. We identified 34 public clonotypes, and structural analysis of two antibodies from a predominant clonotype revealed a common mode of recognition. Thus, vaccination with DS-Cav1 generates a diverse polyclonal response targeting the antigenic sites on pre-F, supporting the development and advanced testing of pre-F-based vaccines against RSV.

PubMed: 33823129
DOI: 10.1016/j.immuni.2021.03.004

Experimental method

X-RAY DIFFRACTION (2.9 Å)