Self-assembled peptide nanofibers raising durable antibody responses against a malaria epitope

Jai S. Rudra, Satish Mishra, Anita S. Chong, Robert A. Mitchell, Elizabeth H. Nardin, Victor Nussenzweig, Joel H. Collier

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

Abstract

Biomaterials that modulate innate and adaptive immune responses are receiving increasing interest as adjuvants for eliciting protective immunity against a variety of diseases. Previous results have indicated that self-assembling β-sheet peptides, when fused with short peptide epitopes, can act as effective adjuvants and elicit robust and long-lived antibody responses. Here we investigated the mechanism of immunogenicity and the quality of antibody responses raised by a peptide epitope from Plasmodium falciparum circumsporozoite (CS) protein, (NANP) 3,conjugated to the self-assembling peptide domain Q11. The mechanism of adjuvant action was investigated in knockout mice with impaired MyD88, NALP3, TLR-2, or TLR-5 function, and the quality of antibodies raised against (NANP) 3-Q11 was assessed using a transgenic sporozoite neutralizing (TSN) assay for malaria infection. (NANP) 3-Q11 self-assembled into nanofibers, and antibody responses lasted up to 40 weeks in C57BL/6 mice. The antibody responses were T cell- and MyD88-dependent. Sera from mice primed with either irradiated sporozoites or a synthetic peptide, (T1BT*) 4-P3C, and boosted with (NANP) 3-Q11 showed significant increases in antibody titers and significant inhibition of sporozoite infection in TSN assays. In addition, two different epitopes could be self-assembled together without compromising the strength or duration of the antibody responses raised against either of them, making these materials promising platforms for self-adjuvanting multi-antigenic immunotherapies.

Original languageEnglish (US)
Pages (from-to)6476-6484
Number of pages9
JournalBiomaterials
Volume33
Issue number27
DOIs
StatePublished - Sep 2012

Keywords

  • Immune response
  • Immunomodulation
  • Immunostimulation
  • Peptide
  • Self-assembly

ASJC Scopus subject areas

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

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