2022
DOI: 10.1038/s41467-022-30222-w
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Quadrivalent mosaic HexaPro-bearing nanoparticle vaccine protects against infection of SARS-CoV-2 variants

Abstract: Emerging SARS-CoV-2 variants of concern (VOCs) harboring multiple mutations in the spike protein raise concerns on effectiveness of current vaccines that rely on the ancestral spike protein. Here, we design a quadrivalent mosaic nanoparticle vaccine displaying spike proteins from the SARS-CoV-2 prototype and 3 different VOCs. The mosaic nanoparticle elicits equivalent or superior neutralizing antibodies against variant strains in mice and non-human primates with only small reduction in neutralization titers ag… Show more

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Cited by 35 publications
(27 citation statements)
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“…In another study, mice immunized with 0.5 or 0.1 μg of SARS-CoV2-2 RBD displayed on SpyCatcher-mi3 nanoparticles induced high titers of neutralizing antibodies that were superior to convalescent sera [ 65 ], demonstrating the neutralizing potency of nanoparticle vaccines even at low doses. Mosaic nanoparticle vaccine candidates co-displaying mutant SARS-CoV-2 spikes have also been developed that induced neutralization of heterologous strains in mice and cynomolgus macaques [ 30 , 66 ]. However, many factors, such as nanoparticle-based antigen safety, longterm stability, and efficacy, need to be thoroughly investigated before advancement into clinical trials.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…In another study, mice immunized with 0.5 or 0.1 μg of SARS-CoV2-2 RBD displayed on SpyCatcher-mi3 nanoparticles induced high titers of neutralizing antibodies that were superior to convalescent sera [ 65 ], demonstrating the neutralizing potency of nanoparticle vaccines even at low doses. Mosaic nanoparticle vaccine candidates co-displaying mutant SARS-CoV-2 spikes have also been developed that induced neutralization of heterologous strains in mice and cynomolgus macaques [ 30 , 66 ]. However, many factors, such as nanoparticle-based antigen safety, longterm stability, and efficacy, need to be thoroughly investigated before advancement into clinical trials.…”
Section: Discussionmentioning
confidence: 99%
“…These findings demonstrate the display efficiency and safety of the encapsulin–SpyTag platform developed by us for antigen presentation. The usage of SpyTag–SpyCatcher system for antigen conjugation to the nanoparticle allows for facile simultaneous display of multiple antigens, as has been previously explored in the case of I53 and mi3 nanoparticles for co-display of spike protein from SARS-CoV-2 variants or zoonotic coronaviruses [ 30 , 66 ]. However, for manufacturing, the necessity of a conjugation step and the presence of unligated material present potential complications.…”
Section: Discussionmentioning
confidence: 99%
“…Zeng et al . [ 377 ] developed a quadrivalent mosaic nanoparticle vaccine that combined four spike proteins, including SARS-CoV-2 prototype and three different variants against COVID-19 infection.…”
Section: Biomaterials Applied In Public Health Emergencymentioning
confidence: 99%
“…The pathogenesis following SARS-CoV-2 infection may comprise acute respiratory distress syndrome and deadly pneumonia, also related to the cytokine storm that induces secondary tissue impairment ( 2 ). Despite the availability of COVID-19 vaccines, clinical evidence shows that emerging mutations result in unexpected escape from vaccine effect ( 3 ). The protection of existing vaccines may be affected over time against the highly infectious Omicron variant ( 4 ).…”
Section: Introductionmentioning
confidence: 99%