Retro-inversion enhances the adjuvant and CpG co-adjuvant activity of host defence peptide Bac2A.
Host defence peptides (HDPs) have a variety of potential therapeutic applications, including as vaccine adjuvants, energizing efforts for modification strategies to address their toxicity and instability. Here we compare l, d and RI-Bac2A as vaccine adjuvants. d and RI-Bac2A are equally resistant to proteolytic degradation with no increases in toxicity, however, only RI-Bac2A maintains adjuvant activity of the natural peptide through conserved induction of a Th2 immune response. As HDPs potentiate the adjuvant activity of CpG ODNs, the isomers were also evaluated as co-adjuvants. l-Bac2A has no significant co-adjuvant activity while CpG/RI-Bac2A induces antibody titres significantly higher than CpG (P<0.01), CpG/l-Bac2A (P<0.01) or CpG/d-Bac2A (P<0.01). None of the isomers influence ODN duration or distribution but l and RI-Bac2A promote ODN uptake into B cells and antigen presenting cells. The enhanced adjuvant and co-adjuvant of RI-Bac2A is hypothesized to result from an undefined combination of increased stability and retained biological activity supporting application of retro-inversion to this, and potentially other HDPs.
Scruten
Erin
E
Vaccine and Infectious Disease Organization, University of Saskatchewan, 120 Veterinary Road, Saskatoon, Saskatchewan S7N 5E3, Canada.
Kovacs-Nolan
Jennifer
J
Griebel
Philip J
PJ
Latimer
Laura
L
Kindrachuk
Jason
J
Potter
Andy
A
Babiuk
Lorne A
LA
Littel-van den Hurk
Sylvia van Drunen
Sv
Napper
Scott
S
D000276:Adjuvants, Immunologic / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000906:Antibodies / Q000097:blood; D002417:Cattle; D005260:Female; D007114:Immunization / Q000379:methods*; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D010047:Ovalbumin / Q000276:immunology; D010447:Peptide Hydrolases / Q000378:metabolism; D010456:Peptides, Cyclic / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D014612:Vaccines / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000906:Antibodies; C408982:CPG-oligonucleotide; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D010456:Peptides, Cyclic; D014612:Vaccines; C056454:bactenecin; D010047:Ovalbumin; D010447:Peptide Hydrolases