1. Nanoparticle display of prefusion coronavirus spike elicits S1-focused cross-reactive antibody response against diverse coronavirus subgenera.
- Author
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Hutchinson GB, Abiona OM, Ziwawo CT, Werner AP, Ellis D, Tsybovsky Y, Leist SR, Palandjian C, West A, Fritch EJ, Wang N, Wrapp D, Boyoglu-Barnum S, Ueda G, Baker D, Kanekiyo M, McLellan JS, Baric RS, King NP, Graham BS, and Corbett-Helaire KS
- Subjects
- Male, Female, Animals, Mice, Antibodies, Viral, Antibody Formation, Epitopes metabolism, Spike Glycoprotein, Coronavirus, Antibodies, Neutralizing, Middle East Respiratory Syndrome Coronavirus, Vaccines
- Abstract
Multivalent antigen display is a fast-growing area of interest toward broadly protective vaccines. Current nanoparticle-based vaccine candidates demonstrate the ability to confer antibody-mediated immunity against divergent strains of notably mutable viruses. In coronaviruses, this work is predominantly aimed at targeting conserved epitopes of the receptor binding domain. However, targeting conserved non-RBD epitopes could limit the potential for antigenic escape. To explore new potential targets, we engineered protein nanoparticles displaying coronavirus prefusion-stabilized spike (CoV_S-2P) trimers derived from MERS-CoV, SARS-CoV-1, SARS-CoV-2, hCoV-HKU1, and hCoV-OC43 and assessed their immunogenicity in female mice. Monotypic SARS-1 nanoparticles elicit cross-neutralizing antibodies against MERS-CoV and protect against MERS-CoV challenge. MERS and SARS nanoparticles elicit S1-focused antibodies, revealing a conserved site on the S N-terminal domain. Moreover, mosaic nanoparticles co-displaying distinct CoV_S-2P trimers elicit antibody responses to distant cross-group antigens and protect male and female mice against MERS-CoV challenge. Our findings will inform further efforts toward the development of pan-coronavirus vaccines., (© 2023. Springer Nature Limited.)
- Published
- 2023
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