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dc.contributor.authorDavenport, Bennett J
dc.contributor.authorCatala, Alexis
dc.contributor.authorWeston, Stuart M
dc.contributor.authorJohnson, Robert M
dc.contributor.authorArdanuy, Jeremy
dc.contributor.authorHammond, Holly L
dc.contributor.authorDillen, Carly
dc.contributor.authorFrieman, Matthew B
dc.contributor.authorCatalano, Carlos E
dc.contributor.authorMorrison, Thomas E
dc.date.accessioned2022-05-31T18:14:14Z
dc.date.available2022-05-31T18:14:14Z
dc.date.issued2022-05-26
dc.identifier.urihttp://hdl.handle.net/10713/19033
dc.description.abstractThe response by vaccine developers to the COVID-19 pandemic has been extraordinary with effective vaccines authorized for emergency use in the United States within 1 year of the appearance of the first COVID-19 cases. However, the emergence of SARS-CoV-2 variants and obstacles with the global rollout of new vaccines highlight the need for platforms that are amenable to rapid tuning and stable formulation to facilitate the logistics of vaccine delivery worldwide. We developed a "designer nanoparticle" platform using phage-like particles (PLPs) derived from bacteriophage lambda for a multivalent display of antigens in rigorously defined ratios. Here, we engineered PLPs that display the receptor-binding domain (RBD) protein from SARS-CoV-2 and MERS-CoV, alone (RBDSARS-PLPs and RBDMERS-PLPs) and in combination (hCoV-RBD PLPs). Functionalized particles possess physiochemical properties compatible with pharmaceutical standards and retain antigenicity. Following primary immunization, BALB/c mice immunized with RBDSARS- or RBDMERS-PLPs display serum RBD-specific IgG endpoint and live virus neutralization titers that, in the case of SARS-CoV-2, were comparable to those detected in convalescent plasma from infected patients. Further, these antibody levels remain elevated up to 6 months post-prime. In dose-response studies, immunization with as little as one microgram of RBDSARS-PLPs elicited robust neutralizing antibody responses. Finally, animals immunized with RBDSARS-PLPs, RBDMERS-PLPs, and hCoV-RBD PLPs were protected against SARS-CoV-2 and/or MERS-CoV lung infection and disease. Collectively, these data suggest that the designer PLP system provides a platform for facile and rapid generation of single and multi-target vaccines.en_US
dc.description.urihttps://doi.org/10.1038/s41541-022-00481-1en_US
dc.language.isoenen_US
dc.publisherSpringer Natureen_US
dc.relationAll data are available in the article and supplementary information. Source data of all data presented in graphs within the figures are provided with the paper.en_US
dc.relation.ispartofNPJ Vaccinesen_US
dc.rights© 2022. The Author(s).en_US
dc.titlePhage-like particle vaccines are highly immunogenic and protect against pathogenic coronavirus infection and disease.en_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41541-022-00481-1
dc.identifier.pmid35618725
dc.source.journaltitleNPJ vaccines
dc.source.volume7
dc.source.issue1
dc.source.beginpage57
dc.source.endpage
dc.source.countryUnited States
dc.source.countryEngland


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