Recent Publication Highlights

Structure-based stabilization of SOSIP Env enhances recombinant ectodomain durability and yield

D. Wrapp, Z. Mu, B. Thakur, K. Janowska, O. Ajayi, M. Barr, R. Parks, K. Mansouri, R.J. Edwards, B.H. Hahn, P. Acharya, K.O. Saunders, B.F. Haynes

The Env glycoprotein is the main focus of HIV vaccine development but due to its inherent metastability, many Env variants are difficult to recombinantly express in the relatively large quantities that are required for biochemical studies and animal trials. Here, we describe a novel structure-based stabilization strategy that works synergistically with previously described SOSIP mutations to dramatically increase the yield of prefusion HIV-1 Env.

A neutralizing human antibody induces movement of the HCoV-229E receptor binding domain

M.F. Liccione, T. Scobey, H.M. Froggatt, C. Pajon, B.L. Yount, Q. Yin, T.N. Spence, E.B. Walter, K.O. Saunders, R.J. Edwards, R.S. Baric, B.F. Haynes, D.W. Cain, T.P. Sheahan, D. Wrapp

The Alphacoronavirus HCoV-229E has been circulating seasonally in the human population for at least 60 years, causing respiratory disease that can sometimes lead to pneumonia. Despite the ubiquity of this endemic pathogen, we still know very little about how the human immune system responds to Alphacoronavirus infection. Here, we describe the first human monoclonal antibodies targeting the HCoV-229E spike, isolated from a convalescent donor. One of these antibodies, DH1533, potently neutralizes a contemporary clinical isolate and cryo-EM analysis of this mAb in complex with HCoV-229E S reveals that it is capable of allosterically inducing movement of neighboring HCoV-229E RBDs.

Selected Publications

Nanoparticle display of prefusion coronavirus spike elicits S1-focused cross-reactive antibody response against diverse coronavirus subgenera (PMID: 37794071)

Engineered immunogens to elicit antibodies against conserved coronavirus epitopes (PMID: 38036525)

A single, improbable B cell receptor mutation confers potent neutralization against cytomegalovirus (PMID: 36662906)

Structural basis for HCMV Pentamer recognition by neuropilin 2 and neutralizing antibodies (PMID: 35275718)

Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein induces genetically and antigenically diverse antibody responses (PMID: 33823129)

Structure-based design of prefusion-stabilized SARS-CoV-2 spikes (PMID: 32703906)

Recognition of a highly conserved glycoprotein B epitope by a bivalent antibody neutralizing HCMV at a post-attachment step (PMID: 32745149)

Structural basis for potent neutralization of betacoronavirus by single-domain camelid antibodies (PMID: 32531248)

Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation (PMID: 32075877)