Oral Presentation International Veterinary Immunology Symposium 2016

Lambda Display Phage as a Mucosal Vaccine Delivery Vehicle for Peptide Antigens (#74)

Philip Griebel 1 , Patricia Gonzalez Cano 1 , Lakshman N Gamage 1 , Connie Hayes 1 , Scott Napper 1 , Sidney Hayes 1
  1. University of Saskatchewan, Saskatoon, SK, Canada

A lack of safe and effective mucosal adjuvants and rapid degradation of vaccine antigens remain major barriers to oral vaccine development for food-producing animals. Bacteriophage possess a unique structural stability in the gastro-intestinal tract that make them ideal candidates as oral vaccine delivery vehicles for immunogenic protein/peptides or DNA vaccines. The safety, stability, ease of production, and immunogenicity of bacteriophages have been characterized but little is known about their capacity to induce mucosal immune responses in the small intestine. Whole body imaging confirmed that within 24 hours orally delivered lambda bacteriophage (LP) were distributed through the gastro-intestinal tract of mice. Targeted delivery of LP to specific sites in the small intestine of newborn calves confirmed LP were immunogenic in a dose-dependent manner. LP were taken up by Peyer’s patches (PPs) and induced LP-specific IgA and T cell responses within the mucosa-associated lymphoid tissue. A lambda display phage (LDP) was constructed to present three immunogenic peptide epitopes (YYR, YML, RL) fused to glycoprotein D (LDP-SJH). Delivery of purified LDP-SJH to surgically constructed intestinal segments induced IgA antibody-secreting cell (ASC) responses to the three peptide epitopes within the targeted PPs. Further, delivery of bacteria expressing D-SJH or bacteria containing assembled LDP-SJH also induced epitope-specific IgA-ASC responses PP. These are the first studies to report the use of LDP to induce epitope-specific mucosal immune responses in the small intestine and confirm that Peyer’s patches function as important site for uptake of LP. Furthermore, immune responses to peptide epitopes displayed on lambda phage were observed in the absence of exogenous immune stimulating compounds or adjuvants. Therefore, we conclude that LDP have substantial potential to be used as safe and effective delivery platforms for the development of oral protein/peptide vaccines.