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SARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung.
Routhu, Nanda Kishore; Cheedarla, Narayanaiah; Bollimpelli, Venkata Satish; Gangadhara, Sailaja; Edara, Venkata Viswanadh; Lai, Lilin; Sahoo, Anusmita; Shiferaw, Ayalnesh; Styles, Tiffany M; Floyd, Katharine; Fischinger, Stephanie; Atyeo, Caroline; Shin, Sally A; Gumber, Sanjeev; Kirejczyk, Shannon; Dinnon, Kenneth H; Shi, Pei-Yong; Menachery, Vineet D; Tomai, Mark; Fox, Christopher B; Alter, Galit; Vanderford, Thomas H; Gralinski, Lisa; Suthar, Mehul S; Amara, Rama Rao.
  • Routhu NK; Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Cheedarla N; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA, USA.
  • Bollimpelli VS; Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Gangadhara S; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA, USA.
  • Edara VV; Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Lai L; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA, USA.
  • Sahoo A; Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Shiferaw A; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA, USA.
  • Styles TM; Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Floyd K; Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA, USA.
  • Fischinger S; Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Atyeo C; Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA, USA.
  • Shin SA; Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Gumber S; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA, USA.
  • Kirejczyk S; Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Dinnon KH; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA, USA.
  • Shi PY; Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Menachery VD; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA, USA.
  • Tomai M; Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Fox CB; Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA, USA.
  • Alter G; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
  • Vanderford TH; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
  • Gralinski L; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
  • Suthar MS; Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Amara RR; Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
Nat Commun ; 12(1): 3587, 2021 06 11.
Article in English | MEDLINE | ID: covidwho-1387350
ABSTRACT
There is a great need for the development of vaccines that induce potent and long-lasting protective immunity against SARS-CoV-2. Multimeric display of the antigen combined with potent adjuvant can enhance the potency and longevity of the antibody response. The receptor binding domain (RBD) of the spike protein is a primary target of neutralizing antibodies. Here, we developed a trimeric form of the RBD and show that it induces a potent neutralizing antibody response against live virus with diverse effector functions and provides protection against SARS-CoV-2 challenge in mice and rhesus macaques. The trimeric form induces higher neutralizing antibody titer compared to monomer with as low as 1µg antigen dose. In mice, adjuvanting the protein with a TLR7/8 agonist formulation alum-3M-052 induces 100-fold higher neutralizing antibody titer and superior protection from infection compared to alum. SARS-CoV-2 infection causes significant loss of innate cells and pathology in the lung, and vaccination protects from changes in innate cells and lung pathology. These results demonstrate RBD trimer protein as a suitable candidate for vaccine against SARS-CoV-2.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Stearic Acids / Adjuvants, Immunologic / COVID-19 Vaccines / COVID-19 / Heterocyclic Compounds, 3-Ring Topics: Vaccines Limits: Animals / Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-23942-Y

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Stearic Acids / Adjuvants, Immunologic / COVID-19 Vaccines / COVID-19 / Heterocyclic Compounds, 3-Ring Topics: Vaccines Limits: Animals / Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-23942-Y