Efficacy of Coxiella burnetii and its chloroform-methanol residue (CMR) fraction against Rift Valley fever virus infection in mice

Strains of Coxiella burnetii phase I and II whole cells (WC-I and WC-II) or whole cell fractions were assessed for their potential to induce long-lasting protection in endotoxin-non-responder C3H/HeJ or CD-1 mice against Rift Valley fever (RVF) virus challenge. Among the whole cell fractions, only the chloroform-methanol residue (CMR), administered as a single dose (100 micrograms per mouse) 24 h before viral challenge, effectively protected 100% of the mice from RVF virus; the CMR of the Ohio strain of C. burnetii was not protective. Most of the RVF virus-infected mice treated with other C. burnetii cell fractions died, although their times to death varied. Lipopolysaccharide (LPS) associated with CMR preparations used in these studies, did not protect against RVF virus challenge. A single dose of 100 micrograms of CMR given 24 h before viral challenge completely eradicated 4-5 logs of RVF virus in the serum, liver, spleen, and central nervous system. Compared to several other immunomodulators, CMR was an equally effective antiviral agent. Efficacy of CMR of both Henzerling and Ohio strains disappeared or was marginal when treatment was initiated 2-3 days before RVF viral challenge, even when a second or a third dose of CMR was administered after challenge. A single dose of liposome-encapsulated CMR to RVF virus-infected mice extended the range of therapeutic efficacy of this biologically active component of C. burnetii to 4 days before infection.