Development of a candidate bacteriophage M13-based vaccine against Rhipicephalus microplus (cattle tick)

Abstract

Cattle tick (Rhipicephalus microplus) related diseases represent as a severe problem in cattle industry worldwide. This ectoparasite has caused huge economic losses in Mexico and around the world, which has been estimated in billions of dollars annually. Currently, the chemical acaricides represents the most widely used control method. However, several problems such as resistance to these drugs and contamination have been associated to this strategy. For such reasons, new approaches have been proposed to control tick infestations. Undoubtedly, the development of a vaccine is the most important of these strategies. Phage-based vaccines represent a fast and low-cost tool for antigen delivery. In this regard, the objective of the present work was to develop a candidate phage-based vaccine displaying a cattle tick antigen (Bm86-derived Sbm7462 antigen) on the surface of bacteriophage M13.

Phage ELISA and dot blotting analysis confirmed the display of the antigen. A 2.73-fold increase in antigen expression was found compared to control (blank). Sbm7462 antigen was expressed in 0.5 µg of protein per 1 × 1011 PFU. Vaccine immunogenicity was evaluated using a bovine monocyte-derived dendritic cell-based ex vivo assay and a murine in vivo assay. The ex vivo model showed the maturation of dendritic cells after being pulsed with the phage-based vaccine (1.5-fold increase in CD80 and 1.6-fold in MHC-II when compared to unstimulated cells). The humoral response was confirmed in the in vivo assay. These results demonstrated the capacity of the phage-based vaccine to induce both humoral and cellular immune-specific responses.

Importantly, this is the first report describing a control method for cattle ticks using a candidate phage-based vaccine. Further studies to evaluate the immunogenicity in a bovine model are needed. Thus, our candidate phage-based vaccine is a promising alternative for the control of cattle ticks.