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Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds.
Wamhoff, Eike-Christian; Ronsard, Larance; Feldman, Jared; Knappe, Grant A; Hauser, Blake M; Romanov, Anna; Case, James Brett; Sanapala, Shilpa; Lam, Evan C; Denis, Kerri J St; Boucau, Julie; Barczak, Amy K; Balazs, Alejandro B; Diamond, Michael S; Schmidt, Aaron G; Lingwood, Daniel; Bathe, Mark.
Affiliation
  • Wamhoff EC; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Ronsard L; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, 02139, USA.
  • Feldman J; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, 02139, USA.
  • Knappe GA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Hauser BM; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Romanov A; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, 02139, USA.
  • Case JB; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Sanapala S; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Lam EC; Department of Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Denis KJS; Department of Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Boucau J; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, 02139, USA.
  • Barczak AK; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, 02139, USA.
  • Balazs AB; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, 02139, USA.
  • Diamond MS; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, 02139, USA.
  • Schmidt AG; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, 02139, USA.
  • Lingwood D; Department of Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Bathe M; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Nat Commun ; 15(1): 795, 2024 Jan 30.
Article in En | MEDLINE | ID: mdl-38291019
ABSTRACT
Protein-based virus-like particles (P-VLPs) are commonly used to spatially organize antigens and enhance humoral immunity through multivalent antigen display. However, P-VLPs are thymus-dependent antigens that are themselves immunogenic and can induce B cell responses that may neutralize the platform. Here, we investigate thymus-independent DNA origami as an alternative material for multivalent antigen display using the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, the primary target of neutralizing antibody responses. Sequential immunization of mice with DNA-based VLPs (DNA-VLPs) elicits protective neutralizing antibodies to SARS-CoV-2 in a manner that depends on the valency of the antigen displayed and on T cell help. Importantly, the immune sera do not contain boosted, class-switched antibodies against the DNA scaffold, in contrast to P-VLPs that elicit strong B cell memory against both the target antigen and the scaffold. Thus, DNA-VLPs enhance target antigen immunogenicity without generating scaffold-directed immunity and thereby offer an important alternative material for particulate vaccine design.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Vaccines, Virus-Like Particle / Spike Glycoprotein, Coronavirus / Antibody Formation Limits: Animals / Humans Language: En Journal: Nat Commun Year: 2024 Document type: Article
Fulltext
Print
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PubMed Links
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Vaccines, Virus-Like Particle / Spike Glycoprotein, Coronavirus / Antibody Formation Limits: Animals / Humans Language: En Journal: Nat Commun Year: 2024 Document type: Article