Recombinant Ehrlichia canis GP19 Protein as a Promising Vaccine Prototype Providing a Protective Immune Response in a Mouse Model

Abstract

The intracellular bacterium Ehrlichia canis is the causative pathogen of canine monocytic ehrlichiosis (CME) in dogs. Despite its veterinary and medical importance, there is currently no available vaccine against this pathogen. In this study, the recombinant GP19 (rGP19) was produced and used as a recombinant vaccine prototype in a mouse model against experimental E. canis infection. The efficacy of the rGP19 vaccine prototype in the part of stimulating B and T cell responses and conferring protection in mice later challenged with E. canis pathogen were evaluated. The rGP19-specific antibody response was evaluated by ELISA after E. canis challenge exposure (on days 0, 7, and 14 post-challenge), and demonstrated significantly higher mean antibody levels in rGP19-immunized mice compared with adjuvant-immunized and naive mice. Significantly lower ehrlichial loads in blood, liver, and spleen DNA samples were detected in the immunized mice with rGP19 by qPCR. The up-regulation of IFNG and IL1 mRNA expression were observed in mice immunized with rGP19. In addition, this study detected IFN-γ-producing memory CD4+ T cells in the rGP19-immunized mice and later infected with E. canis on day 14 post-infection period using flow cytometry. The present study provided a piece of evidence that rGP19 may eliminate E. canis by manipulating Th1 and B cell roles and demonstrated a promising strategy in vaccine development against E. canis infection in the definitive host for further study.

Antibody reactive immunomes of Ehrlichia chaffeensis and E. canis are diverse and defined by conformational antigenic determinants

“…Conventional immunoblotting approaches have helped identify major antibody reactive proteins from E. chaffeensis and E. canis , including major outer membrane proteins (OMPs) ( Ohashi et al., 1998a ; Ohashi et al., 1998b ), tandem repeat proteins (TRPs) ( Doyle et al., 2006 ; McBride et al., 2007 ; Luo et al., 2008 ; Luo et al., 2009 ; McBride et al., 2011 ) and ankyrin repeat proteins (Anks) ( Nethery et al., 2007 ; Luo et al., 2010 ), that contain linear antibody epitopes. Many of these proteins elicit protective immune responses in Ehrlichia infection models ( Li et al., 2001 ; Crocquet-Valdes et al., 2011 ; Kuriakose et al., 2012 ; Nambooppha et al., 2022 ). Moreover, experimental studies have demonstrated protection against infection using live-attenuated vaccines and subunit vaccines ( Rudoler et al., 2012 ; McGill et al., 2016 ; Budachetri et al., 2022 ); however, there are no commercial human or veterinary vaccines available for HME or CME.…”