The use of self-adjuvanting nanofiber vaccines to elicit high-affinity B cell responses to peptide antigens without inflammation

Jianjun Chen, Rebecca R. Pompano, Felix W. Santiago, Lea Maillat, Roger Sciammas, Tao Sun, Huifang Han, David J. Topham, Anita S. Chong, Joel H. Collier

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Balancing immunogenicity with inflammation is a central tenet of vaccine design, especially for subunit vaccines that utilize traditional pro-inflammatory adjuvants. Here we report that by using a nanoparticulate peptide-based vaccine, immunogenicity and local inflammation could be decoupled. Self-assembled β-sheet-rich peptide nanofibers, previously shown to elicit potent antibody responses in mice, were found to be non-cytotoxic invitro and, remarkably, elicited no measurable inflammation invivo-with none of the swelling at the injection site, accumulation of inflammatory cells or cytokines, or production of allergic IgE that were elicited by an alum-adjuvanted vaccine. Nanofibers were internalized by dendritic cells and macrophages at the injection site, and only dendritic cells that acquired the material increased their expression of the activation markers CD80 and CD86. Immunization with epitope-bearing nanofibers elicited antigen-specific differentiation of T cells into T follicular helper cells and B cells into germinal center cells, as well as high-titer, high-affinity IgG that cross-reacted with the native protein antigen and was neutralizing in an invitro influenza hemagglutination inhibition assay. These responses were superior to those induced by alum and comparable to those induced by complete Freund's adjuvant. Thus, nanoparticulate assemblies may provide a new route to non-inflammatory immunotherapies and vaccines.

Original languageEnglish (US)
Pages (from-to)8776-8785
Number of pages10
JournalBiomaterials
Volume34
Issue number34
DOIs
StatePublished - Nov 2013
Externally publishedYes

Fingerprint

Nanofibers
Vaccines
Antigens
Peptides
Subunit Vaccines
B-Lymphocytes
Cells
Inflammation
Dendritic Cells
T Lymphocyte Differentiation Antigens
Injections
Germinal Center
Bearings (structural)
Freund's Adjuvant
Hemagglutination
Helper-Inducer T-Lymphocytes
Immunization
Immunotherapy
Immunoglobulin E
Human Influenza

Keywords

  • Alum adjuvant
  • Nanoparticle vaccines
  • Non-reactogenic
  • OVA(323-339) peptide
  • Self assembly

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

The use of self-adjuvanting nanofiber vaccines to elicit high-affinity B cell responses to peptide antigens without inflammation. / Chen, Jianjun; Pompano, Rebecca R.; Santiago, Felix W.; Maillat, Lea; Sciammas, Roger; Sun, Tao; Han, Huifang; Topham, David J.; Chong, Anita S.; Collier, Joel H.

In: Biomaterials, Vol. 34, No. 34, 11.2013, p. 8776-8785.

Research output: Contribution to journalArticle

Chen, J, Pompano, RR, Santiago, FW, Maillat, L, Sciammas, R, Sun, T, Han, H, Topham, DJ, Chong, AS & Collier, JH 2013, 'The use of self-adjuvanting nanofiber vaccines to elicit high-affinity B cell responses to peptide antigens without inflammation', Biomaterials, vol. 34, no. 34, pp. 8776-8785. https://doi.org/10.1016/j.biomaterials.2013.07.063
Chen, Jianjun ; Pompano, Rebecca R. ; Santiago, Felix W. ; Maillat, Lea ; Sciammas, Roger ; Sun, Tao ; Han, Huifang ; Topham, David J. ; Chong, Anita S. ; Collier, Joel H. / The use of self-adjuvanting nanofiber vaccines to elicit high-affinity B cell responses to peptide antigens without inflammation. In: Biomaterials. 2013 ; Vol. 34, No. 34. pp. 8776-8785.
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