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Design of universal Ebola virus vaccine candidates via immunofocusing.
Xu, Duo; Powell, Abigail E; Utz, Ashley; Sanyal, Mrinmoy; Do, Jonathan; Patten, J J; Moliva, Juan I; Sullivan, Nancy J; Davey, Robert A; Kim, Peter S.
Afiliación
  • Xu D; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305.
  • Powell AE; Sarafan ChEM-H, Stanford University, Stanford, CA 94305.
  • Utz A; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305.
  • Sanyal M; Sarafan ChEM-H, Stanford University, Stanford, CA 94305.
  • Do J; Sarafan ChEM-H, Stanford University, Stanford, CA 94305.
  • Patten JJ; Stanford Medical Scientist Training Program, Stanford University School of Medicine, Stanford, CA 94305.
  • Moliva JI; Stanford Biophysics Program, Stanford University School of Medicine, Stanford, CA 94305.
  • Sullivan NJ; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305.
  • Davey RA; Sarafan ChEM-H, Stanford University, Stanford, CA 94305.
  • Kim PS; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305.
Proc Natl Acad Sci U S A ; 121(7): e2316960121, 2024 Feb 13.
Article en En | MEDLINE | ID: mdl-38319964
ABSTRACT
The Ebola virus causes hemorrhagic fever in humans and poses a significant threat to global public health. Although two viral vector vaccines have been approved to prevent Ebola virus disease, they are distributed in the limited ring vaccination setting and only indicated for prevention of infection from orthoebolavirus zairense (EBOV)-one of three orthoebolavirus species that have caused previous outbreaks. Ebola virus glycoprotein GP mediates viral infection and serves as the primary target of neutralizing antibodies. Here, we describe a universal Ebola virus vaccine approach using a structure-guided design of candidates with hyperglycosylation that aims to direct antibody responses away from variable regions and toward conserved epitopes of GP. We first determined the hyperglycosylation landscape on Ebola virus GP and used that to generate hyperglycosylated GP variants with two to four additional glycosylation sites to mask the highly variable glycan cap region. We then created vaccine candidates by displaying wild-type or hyperglycosylated GP variants on ferritin nanoparticles (Fer). Immunization with these antigens elicited potent neutralizing antisera against EBOV in mice. Importantly, we observed consistent cross-neutralizing activity against Bundibugyo virus and Sudan virus from hyperglycosylated GP-Fer with two or three additional glycans. In comparison, elicitation of cross-neutralizing antisera was rare in mice immunized with wild-type GP-Fer. These results demonstrate a potential strategy to develop universal Ebola virus vaccines that confer cross-protective immunity against existing and emerging filovirus species.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Vacunas Virales / Fiebre Hemorrágica Ebola / Vacunas contra el Virus del Ébola / Ebolavirus Límite: Animals / Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2024 Tipo del documento: Article

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Vacunas Virales / Fiebre Hemorrágica Ebola / Vacunas contra el Virus del Ébola / Ebolavirus Límite: Animals / Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2024 Tipo del documento: Article