Retro-inversion enhances the adjuvant and CpG co-adjuvant activity of host defence peptide Bac2A

• Published in: Vaccine 2010-04, Vol.28 (17), p.2945-2956
• Main Authors: Scruten, Erin, Kovacs-Nolan, Jennifer, Griebel, Philip J, Latimer, Laura, Kindrachuk, Jason, Potter, Andy, Babiuk, Lorne A, Hurk, Sylvia van Drunen Littel-van den, Napper, Scott
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - genetics; Adjuvants, Immunologic - metabolism; Adjuvants, Immunologic - pharmacology; Adjuvants, Immunologic - toxicity; Allergy and Immunology; Animals; Antibodies - blood; Antimicrobial agents; Applied microbiology; Biological activity; Biological and medical sciences; Cattle; CpG ODN; Female; Fundamental and applied biological sciences. Psychology; Host defence peptides; Immune response; Immune system; Immunization - methods; Immunoglobulin G - blood; Inversion; Membranes; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microbiology; Oligodeoxyribonucleotides - pharmacology; Ovalbumin - immunology; Peptide Hydrolases - metabolism; Peptide stabilization; Peptides; Peptides, Cyclic - genetics; Peptides, Cyclic - metabolism; Peptides, Cyclic - pharmacology; Peptides, Cyclic - toxicity; Retro-inversion; Vaccine adjuvant; Vaccines; Vaccines - immunology; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2010.02.015

Abstract 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.