Coxiella burnetii is a Gram-negative bacterium that causes acute and chronic Query fever (Q fever) in humans. Q fever can be asymptomatic or it can cause flu-like symptoms, such as high fever, chills, sweating, fatigue, muscle pain, headache, loss of appetite, nausea and vomiting. These acute symptoms can last one to two weeks. In chronic cases, infected persons can develop liver and heart disease and in some cases Q fever can be fatal. In these chronic cases, a small percentage of patients develop hepatitis or liver disease and jaundice. Another rare symptom is endocarditis, an inflammation of the lining of the heart cavity. Animals such as cattle, sheep and goats can carry C. burnetii in tissues involved in birth, such as the uterus, placenta, and birth fluids. Infected animals also release C. burnetii in milk and manure. Thus, people can acquire Q fever by inhaling infectious aerosols and contaminated dusts generated by animals or through animal products.
C. burnetii is an obligate intracellular Gram-negative bacterium that is an understudied category B select agent and can be transmitted via aerosol. The highly infectious nature of C. burnetii and its hardiness in adverse environmental conditions make this organism an important zoonotic pathogen, and potentially useful in bioterrorism and biological warfare. Since Q fever is a significant occupational hazard among veterinarians, meat processing plant workers, sheep and diary workers, livestock farmers, and researchers at facilities housing sheep, C. burnetii has been used for developing biological weapons in the past, and recently chronic Q fever cases have been increasing worldwide, Q fever is becoming a significant public health concern. Because C. burnetii infection can develop into more severe chronic diseases, vaccination is the logical approach to prevent individuals at risk of natural and deliberate exposure. Although formalin-inactivated C. burnetii phase I (PI) whole-cell vaccine provides near-complete protection in animal models as well as humans, it can induce severe local or systemic adverse reactions when administered to individuals with prior immunity to the agent. A formalin-inactivated whole cell vaccine, Q-vax, has been developed and widely used in high-risk individuals in Australia since 1989. Safe use of this vaccine requires screening of potential vaccines by skin test, serological tests, or in vitro lymphocyte proliferation assay. The time consuming and costly screening procedures limit the use of phase I vaccine (PIV) for a mass vaccination program. Currently, there is no licensed vaccine for preventing Q fever in the United States. Creation of a safe and effective new generation vaccine to prevent Q fever remains an important public health goal.
Based on prior studies, C. burnetii undergoes a lipopolysaccharide (LPS) phase variation in which its virulent smooth LPS phase I (PI) converts to an avirulent rough LPS phase II (PII) upon serial passage in eggs and tissue culture. It has been shown that PI vaccine (PIV) was more protective than PII vaccine (PIIV) in guinea pig and mouse models. An earlier study has shown that PI-LPS is able to elicit antibody (Ab) responses to PI and PII antigens and to confer protection against virulent C. burnetii challenge in a mouse model. One recent study also demonstrated that PI-LPS induced a level of protection similar to PIV, but PII-LPS did not provide measurable protection. Since cultivation of C. burnetii is difficult, hazardous, and requires the use of a BL3 facility, it is very difficult to generate large quantities of purified bacteria for isolation of LPS, which consequently limits the use of C. burnetii LPS to produce vaccines. Thus, a LPS-based Q fever vaccine has not been successful.