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Adjuvanting a subunit COVID-19 vaccine to induce protective immunity.
Arunachalam, Prabhu S; Walls, Alexandra C; Golden, Nadia; Atyeo, Caroline; Fischinger, Stephanie; Li, Chunfeng; Aye, Pyone; Navarro, Mary Jane; Lai, Lilin; Edara, Venkata Viswanadh; Röltgen, Katharina; Rogers, Kenneth; Shirreff, Lisa; Ferrell, Douglas E; Wrenn, Samuel; Pettie, Deleah; Kraft, John C; Miranda, Marcos C; Kepl, Elizabeth; Sydeman, Claire; Brunette, Natalie; Murphy, Michael; Fiala, Brooke; Carter, Lauren; White, Alexander G; Trisal, Meera; Hsieh, Ching-Lin; Russell-Lodrigue, Kasi; Monjure, Christopher; Dufour, Jason; Spencer, Skye; Doyle-Meyers, Lara; Bohm, Rudolph P; Maness, Nicholas J; Roy, Chad; Plante, Jessica A; Plante, Kenneth S; Zhu, Alex; Gorman, Matthew J; Shin, Sally; Shen, Xiaoying; Fontenot, Jane; Gupta, Shakti; O'Hagan, Derek T; Van Der Most, Robbert; Rappuoli, Rino; Coffman, Robert L; Novack, David; McLellan, Jason S; Subramaniam, Shankar.
  • Arunachalam PS; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
  • Walls AC; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Golden N; Tulane National Primate Research Center, Covington, LA, USA.
  • Atyeo C; Ragon Institute of MIT, MGH and Harvard, Cambridge, MA, USA.
  • Fischinger S; Ragon Institute of MIT, MGH and Harvard, Cambridge, MA, USA.
  • Li C; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
  • Aye P; Tulane National Primate Research Center, Covington, LA, USA.
  • Navarro MJ; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Lai L; Yerkes National Primate Research Center, Atlanta, Georgia, USA.
  • Edara VV; Yerkes National Primate Research Center, Atlanta, Georgia, USA.
  • Röltgen K; Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
  • Rogers K; New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, USA.
  • Shirreff L; New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, USA.
  • Ferrell DE; New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, USA.
  • Wrenn S; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Pettie D; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Kraft JC; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Miranda MC; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Kepl E; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Sydeman C; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Brunette N; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Murphy M; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Fiala B; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Carter L; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • White AG; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Trisal M; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Hsieh CL; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Russell-Lodrigue K; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Monjure C; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Dufour J; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Spencer S; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Doyle-Meyers L; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Bohm RP; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Maness NJ; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Roy C; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Plante JA; Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Plante KS; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
  • Zhu A; Department of Molecular Biosciences, University of Texas, Austin, TX, USA.
  • Gorman MJ; Tulane National Primate Research Center, Covington, LA, USA.
  • Shin S; Tulane National Primate Research Center, Covington, LA, USA.
  • Shen X; Tulane National Primate Research Center, Covington, LA, USA.
  • Fontenot J; Tulane National Primate Research Center, Covington, LA, USA.
  • Gupta S; Tulane National Primate Research Center, Covington, LA, USA.
  • O'Hagan DT; Tulane National Primate Research Center, Covington, LA, USA.
  • Van Der Most R; Tulane National Primate Research Center, Covington, LA, USA.
  • Rappuoli R; Tulane National Primate Research Center, Covington, LA, USA.
  • Coffman RL; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA.
  • Novack D; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA.
  • McLellan JS; Ragon Institute of MIT, MGH and Harvard, Cambridge, MA, USA.
  • Subramaniam S; Ragon Institute of MIT, MGH and Harvard, Cambridge, MA, USA.
Nature ; 594(7862): 253-258, 2021 06.
Artículo en Inglés | MEDLINE | ID: covidwho-1192479
ABSTRACT
The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative1. Here we demonstrate the capacity of a subunit vaccine, comprising the SARS-CoV-2 spike protein receptor-binding domain displayed on an I53-50 protein nanoparticle scaffold (hereafter designated RBD-NP), to stimulate robust and durable neutralizing-antibody responses and protection against SARS-CoV-2 in rhesus macaques. We evaluated five adjuvants including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an α-tocopherol-containing oil-in-water emulsion; AS37, a Toll-like receptor 7 (TLR7) agonist adsorbed to alum; CpG1018-alum, a TLR9 agonist formulated in alum; and alum. RBD-NP immunization with AS03, CpG1018-alum, AS37 or alum induced substantial neutralizing-antibody and CD4 T cell responses, and conferred protection against SARS-CoV-2 infection in the pharynges, nares and bronchoalveolar lavage. The neutralizing-antibody response to live virus was maintained up to 180 days after vaccination with RBD-NP in AS03 (RBD-NP-AS03), and correlated with protection from infection. RBD-NP immunization cross-neutralized the B.1.1.7 SARS-CoV-2 variant efficiently but showed a reduced response against the B.1.351 variant. RBD-NP-AS03 produced a 4.5-fold reduction in neutralization of B.1.351 whereas the group immunized with RBD-NP-AS37 produced a 16-fold reduction in neutralization of B.1.351, suggesting differences in the breadth of the neutralizing-antibody response induced by these adjuvants. Furthermore, RBD-NP-AS03 was as immunogenic as a prefusion-stabilized spike immunogen (HexaPro) with AS03 adjuvant. These data highlight the efficacy of the adjuvanted RBD-NP vaccine in promoting protective immunity against SARS-CoV-2 and have led to phase I/II clinical trials of this vaccine (NCT04742738 and NCT04750343).
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Texto completo: Disponible Colección: Bases de datos internacionales Base de datos: MEDLINE Asunto principal: Adyuvantes Inmunológicos / Vacunas de Subunidad / Anticuerpos Neutralizantes / Vacunas contra la COVID-19 / SARS-CoV-2 / COVID-19 Tipo de estudio: Estudio experimental / Estudio pronóstico / Ensayo controlado aleatorizado Tópicos: Vacunas / Variantes Límite: Animales Idioma: Inglés Revista: Nature Año: 2021 Tipo del documento: Artículo País de afiliación: S41586-021-03530-2

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Texto completo: Disponible Colección: Bases de datos internacionales Base de datos: MEDLINE Asunto principal: Adyuvantes Inmunológicos / Vacunas de Subunidad / Anticuerpos Neutralizantes / Vacunas contra la COVID-19 / SARS-CoV-2 / COVID-19 Tipo de estudio: Estudio experimental / Estudio pronóstico / Ensayo controlado aleatorizado Tópicos: Vacunas / Variantes Límite: Animales Idioma: Inglés Revista: Nature Año: 2021 Tipo del documento: Artículo País de afiliación: S41586-021-03530-2