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 journalArticle

93 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Nanofibers
Epitopes
Sporozoites
Antibodies
Peptides
Malaria
Antibody Formation
Assays
Biocompatible Materials
Adaptive Immunity
Plasmodium falciparum
Infection
Inbred C57BL Mouse
Innate Immunity
Knockout Mice
Immunotherapy
Immunity
T-cells
Biomaterials
T-Lymphocytes

Keywords

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

ASJC Scopus subject areas

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

Cite this

Rudra, J. S., Mishra, S., Chong, A. S., Mitchell, R. A., Nardin, E. H., Nussenzweig, V., & Collier, J. H. (2012). Self-assembled peptide nanofibers raising durable antibody responses against a malaria epitope. Biomaterials, 33(27), 6476-6484. https://doi.org/10.1016/j.biomaterials.2012.05.041

Self-assembled peptide nanofibers raising durable antibody responses against a malaria epitope. / Rudra, Jai S.; Mishra, Satish; Chong, Anita S.; Mitchell, Robert A.; Nardin, Elizabeth H.; Nussenzweig, Victor; Collier, Joel H.

In: Biomaterials, Vol. 33, No. 27, 09.2012, p. 6476-6484.

Research output: Contribution to journalArticle

Rudra, JS, Mishra, S, Chong, AS, Mitchell, RA, Nardin, EH, Nussenzweig, V & Collier, JH 2012, 'Self-assembled peptide nanofibers raising durable antibody responses against a malaria epitope', Biomaterials, vol. 33, no. 27, pp. 6476-6484. https://doi.org/10.1016/j.biomaterials.2012.05.041
Rudra JS, Mishra S, Chong AS, Mitchell RA, Nardin EH, Nussenzweig V et al. Self-assembled peptide nanofibers raising durable antibody responses against a malaria epitope. Biomaterials. 2012 Sep;33(27):6476-6484. https://doi.org/10.1016/j.biomaterials.2012.05.041
Rudra, Jai S. ; Mishra, Satish ; Chong, Anita S. ; Mitchell, Robert A. ; Nardin, Elizabeth H. ; Nussenzweig, Victor ; Collier, Joel H. / Self-assembled peptide nanofibers raising durable antibody responses against a malaria epitope. In: Biomaterials. 2012 ; Vol. 33, No. 27. pp. 6476-6484.
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