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

Publication ,  Journal Article
Rudra, JS; Mishra, S; Chong, AS; Mitchell, RA; Nardin, EH; Nussenzweig, V; Collier, JH
Published in: Biomaterials
September 2012

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.

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Published In

Biomaterials

DOI

EISSN

1878-5905

ISSN

0142-9612

Publication Date

September 2012

Volume

33

Issue

27

Start / End Page

6476 / 6484

Related Subject Headings

  • T-Lymphocytes
  • Sporozoites
  • Protein Structure, Secondary
  • Peptides
  • Oligopeptides
  • Nanofibers
  • Myeloid Differentiation Factor 88
  • Molecular Sequence Data
  • Mice, Knockout
  • Mice, Inbred C57BL
 

Citation

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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
Rudra, Jai S., Satish Mishra, Anita S. Chong, Robert A. Mitchell, Elizabeth H. Nardin, Victor Nussenzweig, and Joel H. Collier. “Self-assembled peptide nanofibers raising durable antibody responses against a malaria epitope.Biomaterials 33, no. 27 (September 2012): 6476–84. 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):6476–84.
Rudra, Jai S., et al. “Self-assembled peptide nanofibers raising durable antibody responses against a malaria epitope.Biomaterials, vol. 33, no. 27, Sept. 2012, pp. 6476–84. Epmc, doi:10.1016/j.biomaterials.2012.05.041.
Rudra JS, Mishra S, Chong AS, Mitchell RA, Nardin EH, Nussenzweig V, Collier JH. Self-assembled peptide nanofibers raising durable antibody responses against a malaria epitope. Biomaterials. 2012 Sep;33(27):6476–6484.
Journal cover image

Published In

Biomaterials

DOI

EISSN

1878-5905

ISSN

0142-9612

Publication Date

September 2012

Volume

33

Issue

27

Start / End Page

6476 / 6484

Related Subject Headings

  • T-Lymphocytes
  • Sporozoites
  • Protein Structure, Secondary
  • Peptides
  • Oligopeptides
  • Nanofibers
  • Myeloid Differentiation Factor 88
  • Molecular Sequence Data
  • Mice, Knockout
  • Mice, Inbred C57BL