Biological and immunological properties of Coxiella burnetii vaccines in C57BL/10ScN endotoxin-nonresponder mice

Abstract

Vaccines prepared from Formalin-killed whole cells of Coxiella burnetii (Ohio strain) or from chloroform-methanol residue (CMR) and extract (CME) of such cells were examined for biological and immunological properties in male C57BL/10ScN endotoxin nonresponder mice. Vaccines containing killed whole cells induced a high incidence of gross pathology, as evidenced by liver necrosis, significant splenomegaly, and significant hepatomegaly in mice. The degree and onset of these pathological changes were directly and inversely proportional, respectively, to the dosage of killed organisms administered. Conversely, no splenomegaly, hepatomegaly, or liver necrosis were observed in mice inoculated with CMR or CME. Moreover, killed whole cells were lethal for mice at dosages of 150 to 1,200 micrograms, whereas no deaths were seen in animals given 1,200 micrograms of CMR. In addition, antibodies against phase I and phase II antigens of C. burnetii were detected in the sera of mice inoculated with either whole cells or CMR. Enhanced blastogenic response of splenic lymphocytes was observed when animals were vaccinated with killed whole cells and CMR but not with CME. Moreover, 80 to 90% of mice inoculated with 300 micrograms of the CMR were protected against a lethal challenge of viable rickettsiae, whereas only 50% of the animals given 300 micrograms of killed whole cells were protected. Treatments with CME were essentially without value, since no antibodies were detectable and no significant protection was elicited. Collectively, these results show that, although killed whole cells induced immunity in C57BL/10ScN mice, they induced deleterious tissue reactions, whereas CMR, which also induced immunity, was essentially nondeleterious, based on the parameters employed. These observations suggest that the chloroform-methanol-extractable component(s) is implicated in the deleterious tissue reactions and that the phase I and II antigens may not be involved in the induction of the pathology observed in C57BL/10ScN mice.