Self-assembled peptide nanofibers raising durable antibody responses against a malaria epitope.
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.
Department of Surgery, University of Chicago, Chicago, IL 60637, USA.
Jai S
JS
Rudra
Satish
S
Mishra
Anita S
AS
Chong
Robert A
RA
Mitchell
Elizabeth H
EH
Nardin
Victor
V
Nussenzweig
Joel H
JH
Collier
D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D008288:Malaria / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D009842:Oligopeptides / Q000737:chemistry / Q000276:immunology; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D017433:Protein Structure, Secondary; D034101:Sporozoites / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000913:Antibodies, Protozoan; D000939:Epitopes; D053594:Myeloid Differentiation Factor 88; D009842:Oligopeptides; D010455:Peptides; C052953:(asparaginyl-alanyl-asparaginyl-proline)3