Efficacy of the Rabbit Polyclonal Anti-leptospira Antibody against Homotype or Heterotype Leptospira Infection in Hamster

Leptospirosis, caused by Leptospira, is one of the most important of neglected emerging zoonotic diseases that has important impacts on public health worldwide. Polyclonal antibody (pcAb) therapy is a potential method to process a series of pathogens for which there are limited determination of treatment, such as leptospirosis. First, we evaluated the efficacy of pcAb, derived from the sera of rabbits inoculated with Leptospira, against homotype (Leptospira interrogans serovar Lai) or heterotype (Leptospira interrogans serovar Autumnalis) Leptospira infection in a lethal hamster model. The pcAb treatment improved survival compared to the controls. The histopathology’s of the infected kidney, liver and lung were also examined by hematoxylin and eosin staining. Using real-time quantitative PCR, we determined that most of the leptospires in the primary organs were almost completely removed by pcAb. In the second experiment, treatments, including antibiotic, pcAb, and combination, were started immediately after occurrence of the first serious sickness mouse in any group. No significant difference in survival rate between pcAb group and antibiotic group was found, but the combination therapy group significantly improved survival rate compared to the others (P
Author Summary Leptospirosis, caused by Leptospira, is one of the most important neglected emerging zoonotic diseases that has important impacts on public health worldwide. An urgent need exists for novel therapeutic agents directed against Leptospira without severe side-effects. This study demonstrates the efficacy of a rabbit polyclonal antibody (pcAb) measured by survival rate, pathological changes and Leptospira burden. The pcAb can cure the homologous serotype and heterologous serotype Leptospira lethal infection 48 hours after challenge. We also provide a reference dose of pcAb for treating human or dog leptospirosis. In addition, combination of pcAb with antibiotic improved survival compared to antibiotic group in late treatment of homotype leptospirosis in hamster. However, additional clinical research is needed to identify the efficacy in humans.