Cross-protection between distantly related spotted fever group rickettsiae

Two excellent C3H/HeN mouse models of spotted fever rickettsioses caused by the distantly related organisms, Rickettsia conorii and Rickettsia australis, were utilized to evaluate the possibility of the stimulation of broad cross-protective immunity. Sublethal infection stimulated complete immunity, that is absence of disease, after challenge with a dose of the heterologous Rickettsia that uniformly killed naïve mice. In contrast, heterologous immune sera did not protect mice against a lethal dose (two LD50) of rickettsiae in the mouse toxicity neutralization assay, the standard method for evaluation of rickettsial vaccine potency. These observations suggest that development of a broadly protective vaccine against spotted fever group (SFG) rickettsiae is feasible, and the results indicate that mouse toxicity neutralization is an inappropriate method for evaluation of candidate vaccines.