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

doi:10.1016/j.biomaterials.2012.05.041

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 journal › Article › peer-review

156 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 language	English (US)
Pages (from-to)	6476-6484
Number of pages	9
Journal	Biomaterials
Volume	33
Issue number	27
DOIs	https://doi.org/10.1016/j.biomaterials.2012.05.041
State	Published - Sep 2012
Externally published	Yes

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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10.1016/j.biomaterials.2012.05.041

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@article{4641563d65994032a68ffadaead72183,

title = "Self-assembled peptide nanofibers raising durable antibody responses against a malaria epitope",

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.",

keywords = "Immune response, Immunomodulation, Immunostimulation, Peptide, Self-assembly",

author = "Rudra, {Jai S.} and Satish Mishra and Chong, {Anita S.} and Mitchell, {Robert A.} and Nardin, {Elizabeth H.} and Victor Nussenzweig and Collier, {Joel H.}",

note = "Funding Information: This research was supported in part by the National Institutes of Health (NIBIB) 1R01EB009701 (JHC), NIAID 1R21AI094444 (JHC and ASC), and NIAID R01AI083655 (EHN), and by the Chicago Biomedical Consortium (CBC), with support from the Searle Funds at the Chicago Community Trust. We thank Rita Altszuler for technical assistance with malaria assays. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the CBC. We thank Philip Jung, Ye Tian, and Joshua Gasiorowski for assistance with the TEM, which was performed at the University of Chicago Biophysics Core facility.",

year = "2012",

month = sep,

doi = "10.1016/j.biomaterials.2012.05.041",

language = "English (US)",

volume = "33",

pages = "6476--6484",

journal = "Biomaterials",

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AU - Rudra, Jai S.

AU - Mishra, Satish

AU - Chong, Anita S.

AU - Mitchell, Robert A.

AU - Nardin, Elizabeth H.

AU - Nussenzweig, Victor

AU - Collier, Joel H.

N1 - Funding Information: This research was supported in part by the National Institutes of Health (NIBIB) 1R01EB009701 (JHC), NIAID 1R21AI094444 (JHC and ASC), and NIAID R01AI083655 (EHN), and by the Chicago Biomedical Consortium (CBC), with support from the Searle Funds at the Chicago Community Trust. We thank Rita Altszuler for technical assistance with malaria assays. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the CBC. We thank Philip Jung, Ye Tian, and Joshua Gasiorowski for assistance with the TEM, which was performed at the University of Chicago Biophysics Core facility.

PY - 2012/9

Y1 - 2012/9

N2 - 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.

AB - 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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KW - Immunomodulation

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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