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Phage-like particle vaccines are highly immunogenic and protect against pathogenic coronavirus infection and disease.
Davenport, Bennett J; Catala, Alexis; Weston, Stuart M; Johnson, Robert M; Ardanuy, Jeremy; Hammond, Holly L; Dillen, Carly; Frieman, Matthew B; Catalano, Carlos E; Morrison, Thomas E.
  • Davenport BJ; Department of Immunology and Microbiology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
  • Catala A; Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
  • Weston SM; Program in Structural Biology and Biochemistry, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
  • Johnson RM; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Ardanuy J; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Hammond HL; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Dillen C; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Frieman MB; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Catalano CE; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Morrison TE; Program in Structural Biology and Biochemistry, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Carlos.Catalano@cuanschutz.edu.
NPJ Vaccines ; 7(1): 57, 2022 May 26.
Article in English | MEDLINE | ID: covidwho-1864747
ABSTRACT
The 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.

Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines / Variants Language: English Journal: NPJ Vaccines Year: 2022 Document Type: Article Affiliation country: S41541-022-00481-1

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Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines / Variants Language: English Journal: NPJ Vaccines Year: 2022 Document Type: Article Affiliation country: S41541-022-00481-1