Protective efficacy of whole-cell inactivated Leptospira vaccines made using virulent or avirulent strains in a hamster model

Abstract

Whole-cell inactivated vaccines remain the only licensed vaccines used to control human and animal leptospirosis worldwide. Although they are protective against lethal infections, the efficacy of these vaccines has been divergent. The manufacturing process often involves the use of standard bacterial strains subjected to serial in vitro passages, with a risk of loss of virulence, and may affect the immunogenicity and consequently decrease protection. Thus, the objective of this study was to perform a comparative analysis of the efficacy of in-house bacterins produced with standard (avirulent) and virulent strains. Hamsters were immunized with killed bacteria produced using avirulent and virulent strains of L. interrogans serovars Copenhageni and Canicola. Vaccine efficacy was determined in terms of protection against lethal homologous or heterologous challenges. The results showed that immunization with both avirulent and virulent Canicola strains resulted in 100% protection against homologous challenge. Conversely, Copenhageni bacterins produced using an avirulent strain conferred only 25–37.5% protection against homologous challenge (P > 0.05), while virulent Copenhageni bacterin conferred 100% protection (P < 0.001). A single vaccine dose was sufficient to induce protection, and administration of a prime boost significantly reduced the bacterial load in the kidneys and improved the humoral immune response to the virulent Copenhageni strain. These findings suggest that the maintenance of virulent strains in bacterin formulations is essential for improving the immunogenicity and efficacy of leptospirosis vaccines.