The leptospiral OmpA-like protein (Loa22) is a surface-exposed antigen that elicits bactericidal antibody against heterologous Leptospira

Abstract

Leptospirosis is the most widespread zoonosis, affecting over 1 million humans each year, with more than 60,000 deaths worldwide. Leptospirosis poses a significant health threat to dogs, horses, cattle, and wildlife. The disease may be self-limiting or progress to a life-threatening multi-system disorder affecting the kidneys, liver, and lungs. Currently, bacterin vaccine formulations that consist of one or more laboratory-cultivated strains are used for prevention. However, the antibody response elicited by these vaccines is directed primarily at lipopolysaccharide and is generally serovar-specific. The development of broadly protective subunit vaccines for veterinary and human applications would be a significant step forward in efforts to combat this emerging and antigenically variable pathogen. This study assessed the properties and potential utility of the Leptospira Loa22 (Leptospira OmpA-like 22 kDa protein) protein as a vaccine antigen. Loa22 is a virulence factor that is predicted to transverse the outer membrane and present its N-terminal domain on the cell surface. This report demonstrates that diverse Leptospira strains express Loa22 in vitro and that the protein is antigenic during infection in dogs. Immunoblot and size exclusion chromatography revealed that Loa22 exists in monomeric and trimeric forms. Immunization of rats with recombinant Loa22 elicited bactericidal antibodies against diverse Leptospira strains. The immunodominant bactericidal epitopes were localized within the N-terminal domain using protein-blocking bactericidal assays. This study supports the utility of Loa22, or subfragments thereof, in developing a multivalent chimeric subunit vaccine to prevent leptospirosis and sheds new light on the cellular localization of Loa22.