Molecular basis of antibody mediated immunity against Ehrlichia chaffeensis involves species-specific linear epitopes...

Humoral immune mechanisms are an important component of protective immunity to Ehrlichia species. However, the molecular basis of antibody mediated immunity is not completely defined, and the role of most molecularly characterized major immunoreactive proteins is unknown. In previous studies, we mapped major species-specific continuous epitopes in three surface exposed and secreted tandem repeat proteins (TRP32, TRP47 and TRP120). In this study, we report that protection is provided by antibodies against these molecularly defined TRP epitopes using in vitro and in vivo models. Protection was demonstrated in vitro after prophylactic and therapeutic administration of epitope-specific anti-TRP antibodies, suggesting that the protective mechanisms involve extracellular and intracellular antibody-mediated effects. In vivo passive transfer of individual epitope-specific TRP sera significantly reduced the ehrlichial load and splenomegaly, and protected mice against lethal infection. Moreover, the combination of antibodies to all three TRPs provided enhanced reduction in ehrlichial load similar to that of Ehrlichia chaffeensis immune sera. IgG1 was the predominant antibody isotype in the epitope-specific TRP mouse sera. These results demonstrate that antibodies against linear epitopes in TRP32, TRP47 and TRP120 are protective during E. chaffeensis infection and involves extracellular and intracellular antibody-mediated mechanisms.