Nanoparticle Vaccines Based on the Receptor Binding Domain (RBD) and Heptad Repeat (HR) of SARS-CoV-2 Elicit Robust Protective Immune Responses
Various vaccine strategies have been proposed in response to the global COVID-19 pandemic, each with unique strategies for eliciting immune responses. Here, we developed nanoparticle vaccines by covalently conjugating the self-assembled 24-mer ferritin to the receptor binding domain (RBD) and/or hep...
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Published in | Immunity Vol. 53; no. 6; pp. 1315 - 1330.e9 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article Web Resource |
Language | English |
Published |
United States
Elsevier Inc
15.12.2020
Elsevier BV Elsevier Limited |
Subjects | |
Online Access | Get full text |
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Summary: | Various vaccine strategies have been proposed in response to the global COVID-19 pandemic, each with unique strategies for eliciting immune responses. Here, we developed nanoparticle vaccines by covalently conjugating the self-assembled 24-mer ferritin to the receptor binding domain (RBD) and/or heptad repeat (HR) subunits of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) spike (S) protein. Compared to monomer vaccines, nanoparticle vaccines elicited more robust neutralizing antibodies and cellular immune responses. RBD and RBD-HR nanoparticle vaccinated hACE2 transgenic mice vaccinated with RBD and/or RBD-HR nanoparticles exhibited reduced viral load in the lungs after SARS-CoV-2 challenge. RBD-HR nanoparticle vaccines also promoted neutralizing antibodies and cellular immune responses against other coronaviruses. The nanoparticle vaccination of rhesus macaques induced neutralizing antibodies, and T and B cell responses prior to boost immunization; these responses persisted for more than three months. RBD- and HR-based nanoparticles thus present a promising vaccination approach against SARS-CoV-2 and other coronaviruses.
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•RBD and HR nanoparticle vaccines induce potent neutralizing antibody responses•Nanoparticle vaccines protect against SARS-CoV-2 infection in mice•HR antigens elicit both humoral and cellular immune responses•HR antigens within nanoparticles contribute to cross-protective immunity
Ma et al. construct two Ferritin-based nanoparticle vaccines that conjugate RBD and HR antigens in SARS-CoV-2 Spike protein utilizing the SpyTag/SpyCatcher system. RBD and RBD-HR nanoparticles vaccines elicit more potent neutralizing antibody responses and stronger T cell immune responses than monomers. HR-containing nanoparticles induce cross-reactive immune responses against other coronaviruses. |
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Bibliography: | Lead Contact These authors contributed equally |
ISSN: | 1074-7613 1097-4180 |
DOI: | 10.1016/j.immuni.2020.11.015 |