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A yeast expressed RBD-based SARS-CoV-2 vaccine formulated with 3M-052-alum adjuvant promotes protective efficacy in non-human primates.
Pino, Maria; Abid, Talha; Pereira Ribeiro, Susan; Edara, Venkata Viswanadh; Floyd, Katharine; Smith, Justin C; Latif, Muhammad Bilal; Pacheco-Sanchez, Gabriela; Dutta, Debashis; Wang, Shelly; Gumber, Sanjeev; Kirejczyk, Shannon; Cohen, Joyce; Stammen, Rachelle L; Jean, Sherrie M; Wood, Jennifer S; Connor-Stroud, Fawn; Pollet, Jeroen; Chen, Wen-Hsiang; Wei, Junfei; Zhan, Bin; Lee, Jungsoon; Liu, Zhuyun; Strych, Ulrich; Shenvi, Neeta; Easley, Kirk; Weiskopf, Daniela; Sette, Alessandro; Pollara, Justin; Mielke, Dieter; Gao, Hongmei; Eisel, Nathan; LaBranche, Celia C; Shen, Xiaoying; Ferrari, Guido; Tomaras, Georgia D; Montefiori, David C; Sekaly, Rafick P; Vanderford, Thomas H; Tomai, Mark A; Fox, Christopher B; Suthar, Mehul S; Kozlowski, Pamela A; Hotez, Peter J; Paiardini, Mirko; Bottazzi, Maria Elena; Kasturi, Sudhir Pai.
  • Pino M; Division of Microbiology and Immunology, Yerkes National Primate Research Center at Emory University, 954 Gatewood Rd, Atlanta, GA, U.S.A.
  • Abid T; Division of Microbiology and Immunology, Yerkes National Primate Research Center at Emory University, 954 Gatewood Rd, Atlanta, GA, U.S.A.
  • Pereira Ribeiro S; Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, U.S.A.
  • Edara VV; Division of Microbiology and Immunology, Yerkes National Primate Research Center at Emory University, 954 Gatewood Rd, Atlanta, GA, U.S.A.
  • Floyd K; Emory Vaccine Center at Emory University, 954, Gatewood Rd, Atlanta, GA, U.S.A.
  • Smith JC; Centers for Childhood Infections and Vaccines; Children's Healthcare of Atlanta and Emory University, Department of Pediatrics, Atlanta, GA, U.S.A.
  • Latif MB; Division of Microbiology and Immunology, Yerkes National Primate Research Center at Emory University, 954 Gatewood Rd, Atlanta, GA, U.S.A.
  • Pacheco-Sanchez G; Emory Vaccine Center at Emory University, 954, Gatewood Rd, Atlanta, GA, U.S.A.
  • Dutta D; Centers for Childhood Infections and Vaccines; Children's Healthcare of Atlanta and Emory University, Department of Pediatrics, Atlanta, GA, U.S.A.
  • Wang S; Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, U.S.A.
  • Gumber S; Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, U.S.A.
  • Kirejczyk S; Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, U.S.A.
  • Cohen J; Division of Microbiology and Immunology, Yerkes National Primate Research Center at Emory University, 954 Gatewood Rd, Atlanta, GA, U.S.A.
  • Stammen RL; Division of Microbiology and Immunology, Yerkes National Primate Research Center at Emory University, 954 Gatewood Rd, Atlanta, GA, U.S.A.
  • Jean SM; Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, U.S.A.
  • Wood JS; Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Connor-Stroud F; Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, U.S.A.
  • Pollet J; Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Chen WH; Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Wei J; Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Zhan B; Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Lee J; Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Liu Z; Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Strych U; Texas Children's Center for Vaccine Development, Houston, TX, U.S.A.
  • Shenvi N; Department of Pediatrics, Molecular Virology & Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, U.S.A.
  • Easley K; Texas Children's Center for Vaccine Development, Houston, TX, U.S.A.
  • Weiskopf D; Department of Pediatrics, Molecular Virology & Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, U.S.A.
  • Sette A; Texas Children's Center for Vaccine Development, Houston, TX, U.S.A.
  • Pollara J; Department of Pediatrics, Molecular Virology & Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, U.S.A.
  • Mielke D; Texas Children's Center for Vaccine Development, Houston, TX, U.S.A.
  • Gao H; Department of Pediatrics, Molecular Virology & Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, U.S.A.
  • Eisel N; Texas Children's Center for Vaccine Development, Houston, TX, U.S.A.
  • LaBranche CC; Department of Pediatrics, Molecular Virology & Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, U.S.A.
  • Shen X; Texas Children's Center for Vaccine Development, Houston, TX, U.S.A.
  • Ferrari G; Department of Pediatrics, Molecular Virology & Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, U.S.A.
  • Tomaras GD; Texas Children's Center for Vaccine Development, Houston, TX, U.S.A.
  • Montefiori DC; Department of Pediatrics, Molecular Virology & Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, U.S.A.
  • Sekaly RP; Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, U.S.A.
  • Vanderford TH; Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, U.S.A.
  • Tomai MA; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.
  • Fox CB; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.
  • Suthar MS; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.
  • Kozlowski PA; Duke Human Vaccine Institute and Department of Surgery, Duke University Medical Center Durham, NC, USA.
  • Hotez PJ; Duke Human Vaccine Institute and Department of Surgery, Duke University Medical Center Durham, NC, USA.
  • Paiardini M; Duke Human Vaccine Institute and Department of Surgery, Duke University Medical Center Durham, NC, USA.
  • Bottazzi ME; Duke Human Vaccine Institute and Department of Surgery, Duke University Medical Center Durham, NC, USA.
  • Kasturi SP; Duke Human Vaccine Institute and Department of Surgery, Duke University Medical Center Durham, NC, USA.
Sci Immunol ; 6(61)2021 07 15.
Article in English | MEDLINE | ID: covidwho-1315792
ABSTRACT
Ongoing SARS-CoV-2 vaccine development is focused on identifying stable, cost-effective, and accessible candidates for global use, specifically in low and middle-income countries. Here, we report the efficacy of a rapidly scalable, novel yeast expressed SARS-CoV-2 specific receptor-binding domain (RBD) based vaccine in rhesus macaques. We formulated the RBD immunogen in alum, a licensed and an emerging alum adsorbed TLR-7/8 targeted, 3M-052-alum adjuvants. The RBD+3M-052-alum adjuvanted vaccine promoted better RBD binding and effector antibodies, higher CoV-2 neutralizing antibodies, improved Th1 biased CD4+T cell reactions, and increased CD8+ T cell responses when compared to the alum-alone adjuvanted vaccine. RBD+3M-052-alum induced a significant reduction of SARS-CoV-2 virus in respiratory tract upon challenge, accompanied by reduced lung inflammation when compared with unvaccinated controls. Anti-RBD antibody responses in vaccinated animals inversely correlated with viral load in nasal secretions and BAL. RBD+3M-052-alum blocked a post SARS-CoV-2 challenge increase in CD14+CD16++ intermediate blood monocytes, and Fractalkine, MCP-1, and TRAIL in the plasma. Decreased plasma analytes and intermediate monocyte frequencies correlated with reduced nasal and BAL viral loads. Lastly, RBD-specific plasma cells accumulated in the draining lymph nodes and not in the bone marrow, contrary to previous findings. Together, these data show that a yeast expressed, RBD-based vaccine+3M-052-alum provides robust immune responses and protection against SARS-CoV-2, making it a strong and scalable vaccine candidate.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Adjuvants, Immunologic / Saccharomycetales / Alum Compounds / Spike Glycoprotein, Coronavirus / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 Topics: Vaccines Limits: Animals / Humans / Male Language: English Year: 2021 Document Type: Article Affiliation country: Sciimmunol.abh3634

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Adjuvants, Immunologic / Saccharomycetales / Alum Compounds / Spike Glycoprotein, Coronavirus / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 Topics: Vaccines Limits: Animals / Humans / Male Language: English Year: 2021 Document Type: Article Affiliation country: Sciimmunol.abh3634